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.

Corporate social responsibility of pharmaceutical industry in Korea.

Background: Global pharmaceutical companies in Korea argue that the development of innovative drugs should be recognized as a social contribution, yet it has been countered by various stakeholders. The need to distinguish between philanthropic activities and Corporate Social Responsibility (CSR) of pharmaceutical companies and reaching consensus in the Korean context has been raised. We sought to evaluate the CSR status of Korean pharmaceutical companies and collect the stakeholders' opinions to define philanthropic activities and CSR related to pharmaceutical companies in Korea. Methods: We conducted a literature review on the definition of CSR of pharmaceutical companies, and the CSR activities of the domestic pharmaceutical companies were compared with those of global pharmaceutical companies operating in Korea. The opinions of stakeholder groups (patient advocate groups, consumer organizations, and domestic/global pharmaceutical companies) were collected using focus group interviews (FGI) and written surveys. Results: Literature review suggested that CSR is categorized as "must do" (economic and legal responsibilities), "ought to do" (ethical responsibilities), and "can do" (philanthropic responsibilities), whereas contributions beyond the economic, legal, or ethical responsibilities can be defined as "can do" (philanthropic responsibilities). Domestic pharmaceutical companies simply adopted systems for ethical and ESG (Environmental, Social, and Governance) management, which are at the "ought to do" level (ethical responsibility), whereas the headquarters of these global pharmaceutical companies established the CSR team and systematically reported on the CSR activity, including ESG management reports, which is at the "ought to do" level and further moving to the "can do" level, but the Korean branch rarely has CSR teams, and the CSR activities in Korea were also insufficient. At the FGI, the global pharmaceutical companies argued that CSR activities, such as innovative drug development, should be recognized as similar to philanthropic activities, yet stakeholders besides them suggested that those activities are "can do" rather than being philanthropic. Discussion: We found that the pharmaceutical companies in Korea are attempting to achieve the "ought to do" level (ethical responsibilities) while complying with the "must do" level (legal and economic responsibilities) yet not philanthropic activities. A social consensus regarding the philanthropic responsibilities of pharmaceutical companies in Korea was not reached.

The Impact of Payment Scheme Changes on Medication Adherence and Persistence of Patients Diagnosed with Depression in Korea.

As of 1 July 2018, the Korean National Health Insurance Service (NHIS) changed the fee schedule for individual psychotherapy (IP). We sought to analyze the impact of the IP payment scheme changes on the medication adherence and persistence of patients diagnosed with depression in Korea. We utilized the NHIS claims database from 2017 to 2019. Patients who were newly diagnosed with depression and utilized IP and were prescribed antidepressants during the study period were included. Adherence was measured using the medication possession ratio (MPR), and persistence was measured using the length of therapy (LOT) during the follow-up period. Adherence and persistence during the pre-policy period (before the change of the payment scheme, from January 2018 until June 2018) and the post-policy period (after the change, from July 2018 until December 2019) were compared. During the study period, a total of 176,740 patients with depression were identified. The average MPR significantly increased from 0.20 to 0.33 in the pre- and post-policy periods, respectively (p < 0.001). The average LOT of the patients improved considerably from 36 to 56 days in the pre- and post-policy periods, respectively (p < 0.001). Poisson regression analysis showed that patients with depression who were female, 19-34 years of age (vs. 50-64 years or over 64 years), and in the post-policy period were significantly associated with greater adherence and persistence rates. Payment scheme changes were associated with an increased adherence and persistence of medication use among patients diagnosed with depression.

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

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

Is the male disadvantage real? Cross-national variations in sex gaps in COVID-19 incidence and mortality.

ABSTRACTAlthough the excess male mortality from COVID-19 is well-known, the variations in sex gaps in incidence and mortality across countries and the sources of such variations are not well understood. This study explored the patterns and the sources of variation in the sex gap in COVID-19 incidence and mortality rates across 100 countries where sex-disaggregated cases and deaths were available as of September 2020. Our results show that there is generally a male disadvantage in both incidence and mortality; however, COVID-19 incidence exhibited a lower male disadvantage (1.2 times higher risk for males) than COVID-19 mortality (1.5 times higher risk for males). The extent of male disadvantages in COVID-19 outcomes across countries varied by societal gender inequalities and behavioural factors. Greater gender equality, both socially and behaviourally, was associated with more equal COVID-19 incidence and mortality between men and women. The findings imply that male disadvantages in COVID-19 outcomes, particularly incidence, are socially determined, whereas further investigation is needed to understand behavioural and biological elements yielding a male disadvantage in mortality.

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

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

Aging and direct medical costs of osteoporotic fractures.

INTRODUCTION: This study estimated the direct medical costs of osteoporotic fractures from a large claims database in Korea. MATERIALS AND METHODS: We compared the medical costs of hip, vertebral, and wrist fractures between two age groups (50-64 years vs 65 years and older). We used a generalized linear model to investigate the drivers of osteoporotic fracture medical costs. RESULTS: Hip fractures had the highest costs, regardless of age, followed by vertebral and wrist. The cost of hip fracture was USD 7285 for those aged 65 years and over and USD 6589 for those aged 50-64 years. The length of hospital days was higher in hip fracture patients, regardless of age, followed by vertebral and wrist. As the number of hospitalizations increased, the medical cost increased by 33.0% (p < 0.0001). Patients older than 65 years who were hospitalized for a fracture had a longer total length of hospital stay, compared to patients aged 50-64, regardlessness of the site of the fracture. The cost of treating fractures among those 65 years and older increased by 31.8% compared to those 50-64 years old (p < 0.0001). The direct medical costs increased by 8.6% as the number of fractures increased (p = 0.041). CONCLUSIONS: We identified that osteoporotic fracture-related medical costs and hospitalization days increased with age. Interventions are effective in reducing fracture risk the potential to yield substantial cost savings.

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.

Burden of Osteoporotic Fractures Using Disability-Adjusted Life Years in South Korea.

There is an increase in the number of patients with osteoporotic fractures due to the aging population in Korea. This study investigated the burden of osteoporotic fractures including hip, spine, and wrist fractures in the Korean population by estimating disability-adjusted life years (DALYs). The DALY for a given condition in a population captures years of life lost due to premature death and years of life lived with a disability and its severity and duration. To calculate DALYs from all relevant data collected for the 3 conditions, we used a DALY calculation template provided by the World Health Organization in 2014. DALYs per 100 000 for vertebral fractures (3168) were higher than those of hip fractures (2496) in women. Wrist fractures (1038) had the least burden, and the difference between men and women was the lowest. The aging population is expected to increase the burden of osteoporosis.

Health state utility values of osteoporotic fractures among Korean women.

Objectives: This study aimed to investigate health state utility values in eight health states related to osteoporosis and osteoporotic fractures using time trade-off (TTO) technique among postmenopausal Korean women.Methods: Scenarios describing eight health states including osteoporosis and hip, vertebral, post-hip, post-vertebral, ankle, humerus, and wrist fractures were developed and presented to 500 female participants aged 45 to 59 years who were selected with probability proportionate to age group and region for this investigation. Each health states valuation was derived using the trade-off (TTO) technique. Ten years of a given health state was traded off with a shorter length of time in full health.Results: Mean scores of each state were calculated. Osteoporosis scored the highest (0.669 ± 0.155), followed by wrist fracture (0.656 ± 0.151). Hip (0.298 ± 0.158) and vertebral (0.298 ± 0.160) fractures were found to be the worst health states. Post-hip (0.446 ± 0.159) and post-vertebral fractures (0.455 ± 0.160) were also considered undesirable states. All fractures were associated with disutilities, ranging from a mean of -0.013 to -0.371. These values were statistically significant (p < 0.0001). Hip and vertebral fractures are among the most serious consequences of osteoporotic fractures.Conclusions: The vertebral and hip fractures marked the lowest utility scores among post-menopausal women in Korea.

Unique health identifiers for universal health coverage.

Identifying everyone residing in a country, especially the poor, is an indispensable part of pursuing universal health coverage (UHC). Having information on an individuals' financial protection is also imperative for measuring the progress of UHC. This paper examines different ways of instituting a system of unique health identifiers that can lead toward achieving UHC, particularly in relation to utilizing universal civil registration and national unique identification number systems. Civil registration is a fundamental function of the government that establishes a legal identity for individuals and enables them to access essential public services. National unique identification numbers assigned at birth registration can further link their vital event information with data collected in different sectors, including in finance and health. Some countries use the national unique identification number as the unique health identifier, such as is done in South Korea and Thailand. In other countries, a unique health identifier is created in addition to the national unique identification number, but the two numbers are linked; Slovenia offers an example of this arrangement. The advantages and disadvantages of the system types are discussed in the paper. In either approach, linking the health system with the civil registration and national identity management systems contributed to advancing effective and efficient UHC programs in those countries.

Disability Weights for Osteoporosis and Osteoporotic Fractures in South Korea.

BACKGROUND: Korea is expected to become an ultra-aged society, in which the elderly population will account for more than 20% of the total population, after 2025. Thus, the social costs due to osteoporotic fractures are expected to increase. Therefore, this study aimed to measure disability weights (DWs) of osteoporosis and osteoporotic fractures in Korea. METHODS: The scenarios were developed to standardize the severity of 6 health statuses: osteoporosis and osteoporotic fractures including wrist, hip, post-hip, vertebral, and post-vertebral fracture. The values for these 6 health statuses were sought via a person trade-off (PTO) approach. We measured the value by PTO and we calculated it to DW of 6 health statuses. Three clinical expertise panels of 33 experts were established, and face-to-face interviews were conducted from July to December 2017. RESULTS: The distribution of DW varied by panel. DWs ranged from 0.5 (Osteoporosis) to 0.857 (Hip fracture) for Panel 1, 0.091 (Osteoporosis) to 0.5 (Hip fracture) for Panel 2, and 0.091 (Osteoporosis) to 0.726 (Hip fracture) for Panel 3. The final values for the 6 health statuses obtained by pooling all data from 3 panels ranged from 0.286 (Osteoporosis) to 0.750 (Hip fracture). There was no significant difference in rankings for the 6 health statuses among the 3 panels. CONCLUSIONS: Comparing the DW of osteoporotic fracture in this study with other diseases in previous studies, it is predicted that osteoporotic fractures, especially hip fractures, will have a considerable burden of disease.

Between government policy, clinical autonomy, and market demands: a qualitative study of the impact of the Prescribing Analysis System on behavior of physicians in South Korea.

BACKGROUND: In South Korea, the Health Insurance Review and Assessment Service manages the Prescribing Analysis System (PAS) to evaluate the appropriate use of medication. To achieve the system's goal of changing prescribing behavior, it is critical to understand how physicians respond to the PAS. This study analyzes the opinions of South Korean physicians about the PAS, the way it is used, and factors affecting prescribing behavior. METHODS: A qualitative, exploratory approach was used, with four focus groups of physicians from different specialties. A semi-structured guide was used to explore their opinions. Transcripts of the discussions were analyzed by the authors, who independently considered content using uniform categories. Common themes were extracted and used to gather results and draw conclusions. RESULTS: Physicians acknowledged some positive aspects of the PAS but, overall, had mainly negative impressions of the system, and particularly, the evaluation reports that it generates. They reported that their prescribing behavior was affected by predisposing factors, including experiential, environmental and psychological factors. Physicians reported that their negative perceptions regarding the regulations were primarily influenced by concerns about maintaining their autonomy and expertise. However, their strong resistance to these perceived infringements on their independence may be considered inconsistent in relation to their professional autonomy as there was an equally strong concern about market competition. Physicians' objections to the PAS are more likely to have been caused by deeply rooted distrust of the government agency in charge of the system. DISCUSSION: Interestingly, we found that physicians' strong resistance to perceived violations of their autonomy seems somewhat inconsistent and contradictory. While they are very positive about new information or printed materials provided by pharmaceutical representatives, they are less enthusiastic when it comes to governmental guidelines or standards. Similarly, they appear to willingly accept situations in which they believe they should comply with patients' demands as a means of surviving in a competitive market. It is notable that physicians' negative perceptions of PAS seemed to be aggravated by suspicion and distrust regarding the purpose of this program. CONCLUSIONS: Because of widespread beliefs in professional autonomy, market competition, and a deep-seated distrust of the system, it would be difficult for the government to persuade physicians to change their prescribing behaviors using only the PAS. Successful implementation of the PAS will not only require its improvement as a policy tool, but also the creation of a social consensus regarding the PAS.

Same drugs, valued differently? Comparing comparators and methods used in reimbursement recommendations in Australia, Canada, and Korea.

To investigate whether the value of the same drug is evaluated differently across jurisdictions, publicly available reimbursement recommendation data from the Health Insurance Review and Assessment Service (HIRA, Korea) from January 2007 until July 2012 were compared with reimbursement recommendation data from the Pharmaceutical Benefit Advisory Committee (PBAC) of Australia, and the Common Drug Review (CDR) and the pan-Canadian Oncology Drug review (pCODR) of Canada. The most recent guidelines from the three agencies regarding the recommended methods of economic evaluation and comparator selection were also compared. During the observation period, 25 products were evaluated by all three countries. No significant differences in the comparator(s)' selection or methods of economic evaluation were found, but the CDR was significantly less likely to positively recommend products compared with the other agencies (p=0.023). The agreement between agencies on selected comparator(s) was moderate to significant (kappa statistics=0.590-0.669), whereas the reimbursement decisions (kappa statistics=0.042-0.296) and the methods of economic evaluation (kappa statistics=0.138-0.525) showed slight to fair agreement. We illustrated that the divergence in reimbursement decisions across jurisdictions is less related to comparator selection or the level of clinical evidence considered and more related to country-specific issues.

Effective policy initiatives to constrain lipid-lowering drug expenditure growth in South Korea.

BACKGROUND: The rapid growth of prescription drug expenditures is a major problem in South Korea. Accordingly, the South Korean government introduced a positive listing system in 2006. They also adopted various price reduction policies. Nevertheless, the total expenditure for lipid-lowering drugs have steadily increased throughout South Korea. The present study explores the factors that have influenced the increased expenditures of lipid-lowering drugs with a particular focus on the effects of statins in this process. METHODS: This paper investigates the National Health Insurance claims data for prescribed lipid-lowering drugs collected between January 1, 2005 and December 31, 2009. We specifically focused on statins and assessed the yearly variation of statin expenditure by calculating the increased rate of paired pharmaceutical expenditures over a 2 year period. Our study classified statins into three categories: new entrants, core medicines and exiting medicines. For core medicines, we further examined influencing factors such as price, amount of drugs consumed by volume, and prescription changes (substitutes for other drug). RESULTS: Statin expenditure showed an average annual increase of 25.7% between 2005 and 2009. Among the different statins, the expenditure of atorvastatin showed a 36.6% annual increase rate, which was the most dramatic among all statins. Also we divided expenditure for core medicines by the price factor, volume factor, and prescription change. The result showed that annual weighted average prices of individual drug decreased each year, which clearly showed that price influenced statin expenditure in a negative direction. The use of generic drugs containing the same active ingredient as name-brand drugs increased and negatively affected statin expenditure (Generic Mix effect). However, the use of relatively expensive ingredients within statin increase, Ingredient Mix effect contributed to increased statin expenditure (Ingredient Mix effect). In particular, the volume effect was found to be critical for increasing statin expenditure as the amount of statin consumed increased steadily throughout the study period. CONCLUSIONS: The recent rapid increase in statin expenditure can largely be attributed to an increase in consumption volume. In order to check drug expenditures effectively in our current situation, in which chronic diseases remain steadily on the rise, it is necessary to not only have supply-side initiatives such as price reduction, but also demand-side initiatives that could control drug consumption volume, for example: educational programs for rational prescription, generic drug promotional policies, and policies providing prescription targets.

Two new stereoisomers of neolignan and lignan from the flower buds of Magnolia fargesii.

A new stereoisomer of 8-O-4' system neolignan, (7R,8S)-1-(3,4-dimethoxyphenyl)-2-[4-(3-hydroxy-1-propenyl)-2-methoxyphenoxy]-propane-1,3-diol (1) and a new stereoisomer of tetrahydrofuranoid lignan, (7R,8S,7'S,8'R)-(3,4,5,3',4')-pentamethoxy-9,7'-dihydroxy-8.8',7.O.9'-lignan (2) along with seven known lignans and neolignans (3-9) were isolated from the methanol extracts of the flower buds of Magnolia fargesii. The structures of these compounds (1-9) were elucidated by spectroscopic methods including 1D- and 2D-NMR as well as by comparison with reported values. Absolute configurations of new stereoisomers 1 and 2 were determined by circular dichroism (CD) spectra. The absolute configuration of (7S,8S,10S)-[tetrahydro-4-hydroxy-2-(3,4,5-trimethoxyphenyl)furan-3-yl]methyl 3,4-dimethoxy benzoate (3) was determined by Mosher's esterification method for the first time in this study. Three lignans, tanegool (4), (+)-dehydrodiconiferyl alcohol (5), and epieudes-min (6), were isolated from this plant for the first time. Superoxide radical scavenging activities of the isolates (1-9) were measured by irradiated riboflavin/ethylenediaminetetraacetic acid (EDTA)/Nitroblue tetrazolium (NBT) system, and their in vitro rat lens aldose reductase (RLAR) inhibitory activities were also evaluated.

Identification of nyasol and structurally related compounds as the active principles from Anemarrhena asphodeloides against respiratory syncytial virus (RSV).

Three known phenolic compounds, (-)-(R)-nyasol (= 4,4'-(1Z,3R)-Penta-1,4-diene-1,3-diyldiphenol; 1), its derivative 2, and broussonin A (3)--isolated from the rhizomes of Anemarrhena asphodeloides--were for the first time identified as the active principles capable of efficient respiratory-syncytial-virus (RSV) inhibition. The IC50 values of 1-3 against the RSV-A2 strain, propagated in HEp-2 cells, were determined, their activities being higher than that of the standard antiviral drug ribavirin (IC50 = 1.15 microM). In addition, the known, but inactive, compound 'trans-N-(para-coumaroyl)tyramine' (= (2E)-3-(4-hydroxyphenyl)-N-[2-(4-hydroxyphenyl)ethyl]prop-2-enamide; 4) was isolated from this plant for the first time.