Quarantining: a mentally distressful but physically comfortable experience in South Korea.

OBJECTIVE: Quarantine is the first response to the COVID-19 pandemic. Restricting daily life can cause several problems. This study aimed to measure the impact of the COVID-19 quarantine on health-related quality of life (HRQoL) by comparing to the pre-pandemic. METHODS: HRQoL during COVID-19 quarantine was surveyed online using EQ-5D index and matched to that of the pre-pandemic-extracted from nationwide representative data of the Korea Community Health Survey- with propensity scores. A beta regression for the EQ-5D scores and a logistic analysis for individual dimensions of the EQ-5D index were performed to measure the impact of the COVID-19 quarantine on health utility. RESULTS: The overall scores of the EQ-5D index were significantly higher in the group under quarantine during the COVID-19 pandemic (0.971 SD 0.064) than those before the pandemic (0.964 SD 0.079, Diff. 0.007 SD 0.101, p = 0.043). The beta regression for the overall scores of EQ-5D revealed that quarantining during the COVID-19 pandemic increased by 52.7% compared to normal life before the outbreak(p = 0.045). Specifically, "Depression/Anxiety" deteriorated significantly during quarantining (OR = 0.62, 95% CI:0.48-0.80). However, "Pain/Discomfort" and "Mobility" significantly improved (OR = 5.37, 95% CI:3.71-7.78 and OR = 2.05, 95% CI:1.11-3.80, respectively). CONCLUSION: Although the world is facing a challenging moment that it has never been through before, mandatory quarantine has served as an experience that provided mental distress but physical comfort in the Korean context.

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.

Bisphosphonates Use and Risk of Subtrochanteric and Diaphyseal Femur Fractures in Korea: Results from the National Claim Registry.

Although Asian with bisphosphonate has been considered to have higher risk of subtrochanteric and diaphyseal femur (ST/DF) fractures, the occurrence of those fractures has been still unclear in Asia. The purpose of this study was to investigate the incidence rate of ST/DF fractures among bisphosphonate users from nationwide database in South Korea. Using national health insurance claim database, we only included the bisphosphonate users who took bisphosphonate for the first time in 2008 and evaluated the incidence rate of ST/DF fracture from 2008 to 2013. Non-user controls were matched to bisphosphonate users by propensity score matching with age and gender. Cox regression models were used to calculate hazard ratios of ST/DF fracture with and without adjustment for comorbidity. A total of 682 ST/DF fractures were observed among 348,311 bisphosphonate users. The incidence rate of ST/DF fracture among bisphosphonate users (37.75/100,000 person years, 95% CI 35.02-40.70) was higher compared with non-users (24.41/100,000 person years, 95% CI 22.31-26.71). The risk of ST/DF fracture was greater in bisphosphonate users compared with non-users (hazard ratio 1.541, 1.370-1.734; p < 0.001). The incidence rate of ST/DF fracture after bisphosphonate use could be determined in Korean patients, which can provide basal information for further studies on risk and benefit of continuing bisphosphonate.

Do newly marketed generic medicines expand markets using descriptive time series analysis and mixed logit models? Korea as an exemplar and its implications.

BACKGROUND: There have been concerns in Korea that the availability of cheaper generics can appreciably increase prescribed volumes thereby negating their beneficial effects on overall pharmaceutical expenditure. Consequently, this study aimed to explore market changes after newly entered generics including market expansion and substitution effects, and to examine factors contributing to the prescribing of newly entered generics using atorvastatin as an exemplar. This is because previous studies have shown market expansion had occurred following generic atorvastatin. METHODS: Explore market expansion effects by extracting all statins users from July 2008 to June 2010 from the nationally representative dataset of 2008, combined with the National Health Insurance Claims data, with atorvastatin's patent expiring in July 2008. The data consisted of medical visit episodes of patients who had been prescribed statins at least once during the observational period. Patients who had been prescribed any statin before the observation period were classified as the previously treated group and those who had not as the newly treated group. Descriptive time series analysis was conducted and the mixed logit model applied to understand factors contributing to generic atorvastatin prescriptions. RESULTS: Market expansion was observed after generic atorvastatin availability with an appreciable increase in number of newly treated patients, whereas substitution effect was found among previously treated patients. Newly treated patients tended to get significantly lower daily doses (p < 0.0001). According to the mixed logistic analysis, newly treated patients were more likely to be prescribed generic atorvastatin (OR = 2.58; 95% CI, 2.05-3.26) than their counterparts. Clinicians and secondary hospitals were also key drivers of generic atorvastatin (ORs were 10.41 and 9.81, respectively). CONCLUSIONS: Newly marketed generic statins in Korea resulted in an expanding market by substantially increasing the number of new patients with clinics and hospitals appreciably using newly marketed generics. However lower doses of statins were prescribed. Policy makers do recognize that generic availability can save costs so should be encouraged. However, this is a concern when generic availability appreciably expands the market, potentially increasing the financial burden. This needs to be addressed. Additionally in Korea, the quality of prescribing should be monitored, especially focusing on clinics and secondary hospitals.

CONSTITUTIVE PHOTOMORPHOGENIC 10 (COP10) Contributes to Floral Repression under Non-Inductive Short Days in Arabidopsis.

In Arabidopsis, CONSTITUTIVE PHOTOMORPHOGENIC/DE-ETIOLATED/FUSCA (COP/DET/FUS) genes act in repression of photomorphogenesis in darkness, and recent reports revealed that some of these genes, such as COP1 and DET1, also have important roles in controlling flowering time and circadian rhythm. The COP/DET/FUS protein COP10 interacts with DET1 and DNA DAMAGE-BINDING PROTEIN 1 (DDB1) to form a CDD complex and represses photomorphogenesis in darkness. The cop10-4 mutants flower normally in inductive long days (LD) but early in non-inductive short days (SD) compared with wild type (WT); however, the role of COP10 remains unknown. Here, we investigate the role of COP10 in SD-dependent floral repression. Reverse transcription-quantitative PCR revealed that in SD, expression of the LD-dependent floral inducers GI, FKF1, and FT significantly increased in cop10-4 mutants, compared with WT. This suggests that COP10 mainly regulates FT expression in a CO-independent manner. We also show that COP10 interacts with GI in vitro and in vivo, suggesting that COP10 could also affect GI function at the posttranslational level. Moreover, FLC expression was repressed drastically in cop10-4 mutants and COP10 interacts with MULTICOPY SUPPRESSOR OF IRA1 4 (MSI4)/FVE (MSI4/FVE), which epigenetically inhibits FLC expression. These data suggest that COP10 contributes to delaying flowering in the photoperiod and autonomous pathways by downregulating FT expression under SD.

Is the Availability of Biosimilar Adalimumab Associated with Budget Savings? A Difference-in-Difference Analysis of 14 Countries.

OBJECTIVE: The aim was to assess the influence of the presence of biosimilar adalimumab on adalimumab budget savings in 14 high- and upper-middle-income countries. METHODS: This study analyzed Multinational Integrated Data Analysis System (MIDAS)-IQVIA data from the fourth quarter (Q4) of 2018 to the Q4 of 2019, comparing adalimumab expenditure (in United States dollars) and consumption (in standard units [SU]) across 14 countries (Australia, Austria, Brazil, Canada, France, Germany, Italy, Japan, Korea, Singapore, South Africa, Spain, Sweden, and Taiwan). The countries were divided into two groups based on the availability of adalimumab biosimilars during the study period. A difference-in-difference design was employed to analyze the groups, focusing on changes from Q4 2018 to Q4 2019. Additionally, changes in adalimumab expenditure were decomposed into price, quantity, and drug mix during the study period. RESULTS: Among countries with adalimumab biosimilars, there was a significant decrease in expenditure (- $371.0 per gross domestic product per capita; p = 0.03) over four quarters, while the consumption significantly increased (1.0 SU per 1000 population; p = 0.02). This was consistent with visual observations and differed from countries without adalimumab biosimilar. Sensitivity analysis with a narrowed list of countries (12 high-income countries) showed a consistent trend. Adalimumab expenditure decreased by 14% during the study period in countries where adalimumab biosimilars were available, mainly due to the price changes (Pt = 0.85; - 15%) and the drug-mix effect (εt  = 0.88; - 12%). Yet, adalimumab expenditure (Et = 1.04; +4%) changed in a quantity-dependent manner (Qt = 1.06; +6%) in countries where adalimumab biosimilars were absent. CONCLUSION: The availability of biosimilars was associated with a decrease in adalimumab expenditure without compromising the consumption of adalimumab.

The feasibility of MR elastography with transpelvic vibration for localization of focal prostate lesion.

We aimed to evaluate the feasibility of MR elastography (MRE) using a transpelvic approach. Thirty-one patients who underwent prostate MRE and had a pathological diagnosis were included in this study. MRE was obtained using a passive driver placed at the umbilicus and iliac crests. The shear stiffness, clinical data, and conventional imaging findings of prostate cancer and benign prostatic hyperplasia (BPH) were compared. Inter-reader agreements were evaluated using the intraclass coefficient class (ICC). Prostate MRE was successfully performed for all patients (100% technical success rate). Nineteen cancer and 10 BPH lesions were visualized on MRE. The mean shear stiffness of cancer was significantly higher than that of BPH (5.99 ± 1.46 kPa vs. 4.67 ± 1.54 kPa, p = 0.045). One cancer was detected on MRE but not on conventional sequences. Six tiny cancer lesions were not visualized on MRE. The mean size of cancers that were not detected on MRE was smaller than that of cancers that were visible on MRE (0.8 ± 0.3 cm vs. 2.3 ± 1.8 cm, p = 0.001). The inter-reader agreement for interpreting MRE was excellent (ICC = 0.95). Prostate MRE with transpelvic vibration is feasible without intracavitary actuators. Transpelvic prostate MRE is reliable for detecting focal lesions, including clinically significant prostate cancer and BPH.

Who persistently consumes dietary supplements? A multifaceted analysis using South Korea's nationally representative health and nutrition examination survey data.

Objective: This study aimed to identify multifaceted factors affecting intake of dietary supplements among Koreans. Methods: Korean National Health and Nutrition Examination Survey (KNHANES) data from 2018 to 2020 were obtained, pertaining to functional food intake, health related behaviors and morbidities. A total of 12,031 participants representing the Korean adult population were identified into two groups: 1 year more consumer group (N = 4,345) vs. non-consumer group (N = 7,686). A logistic regression analysis was performed to analyze the predictors of dietary supplement consumptions. Results: Sociodemographic variables were associated with dietary supplement use. Participants who were female (odds ratio [OR] = 1.85; 95% CI, 1.59-2.15), older (OR = 1.06; 95% CI, 1.04-1.08), married (OR = 6.39; 95% CI, 3.44-11.85), highly educated, and high income earners consumed significantly more dietary supplements. Non-smoking (OR = 1.27; 95% CI, 1.06-1.53) and performing aerobic exercise (OR = 1.28; 95% CI, 1.13-1.46) predict dietary supplement consumption. Self-rated health status and health-related quality of life increased the likelihood of dietary supplement intake by 1.86 (OR = 1.86; 95% CI, 1.04-3.32) and 7.77 times (OR = 7.77; 95% CI, 1.66-33.40), respectively. The number of chronic diseases, cancer, or stroke was not significantly associated with intake. Those with obesity tended to less consume dietary supplements (OR = 0.85; 95% CI, 0.74-0.97). Hypertension (OR = 3.14; 95% CI, 1.36-7.21), osteoporosis (OR = 1.47; 95% CI, 1.11-1.95), and asthma (OR = 0.44; 95% CI, 0.27-0.73) were significantly associated with the intake. Conclusion: Considering that healthy behaviors and subjective health led to the consumption of dietary supplements, whereas current disease or catastrophic experience did not, the intake of dietary supplements should be included in health promotion in Korea.

Introduction of managed entry agreements in Korea: Problem, policy, and politics.

Objectives: This study aimed to understand Managed Entry Agreements (MEAs) in Korea through the framework of three streams of the policy window model and its practical management and impact on pricing and reimbursement scheme. Methods: An extensive literature review based on Kingdon's model was conducted. We also performed descriptive analyses of MEA implementation using data on medicines listed in Korea and compared its MEA scheme with four different countries. Results: As per problem streams, patients with rare disease or cancers have considerable difficulties in affording their medicines and this has challenged the drug benefit system and raised an issue of patient's access. Policy streams highlighted that MEAs were introduced as a benefit enhancement plan for four major diseases since January 2014. MEAs have also been strengthened as a bypass mechanism to expand the insurance coverage especially for new premium-priced medicines under Moon Care (Listing all non-listed services). In descriptive analysis of MEAs, a total of 48 medicines were contracted as MEAs from January 2014 to December 2020, accounting for 73.4% of listed medicines for cancer or rare diseases and 97.9% of the cases were finance-based contracts. Meanwhile, outcome-based contracts such as CED accounted for only 2.1%. The application of MEAs differs across countries, resulting in a kappa coefficient of 0.00-0.14 (United Kingdom 0.03, Italy 0.00, Australia 0.14), indicating a lack of consistency compared to South Korea. Conclusion: MEAs, which were introduced as a bypass mechanism, have now superseded the standard process for anticancer agents or orphan drugs. Further studies are needed to evaluate the impact of the confidential agreements and effectiveness of new high-priced medicines with limited clinical data at launch.

For Whom the Price Escalates: High Price and Uncertain Value of Cancer Drugs.

The price of cancer drugs has skyrocketed, yet it is not clear whether their value is commensurate with their price. More cancer drugs are approved under expedited review, which considers less rigorous clinical evidence, yet only 20% of them show an overall survival gain in the confirmatory trial. Moreover, clinical data are often generated based on small, single-arm studies with surrogate outcomes, challenging economic evaluation. With their high price and uncertain (marginal) clinical value, cancer drugs are frequently rejected by health technology assessment (HTA) bodies. Therefore, agencies, including the UK's National Institute for Health and Care Excellence (NICE), have adopted cancer drug funds (CDF) or risk-sharing schemes to provide extra access for expensive cancer drugs which fail to meet NICE's cost effectiveness threshold. With rising pricing and fewer new cancer medications with novel mechanisms of action, it is unclear if newly marketed cancer therapies address unmet clinical needs or whether we are paying too much. Transparency, equity, innovativeness, and sustainability are all harmed by a "special" approach for cancer medications. If early access is allowed, confirmatory trials within a certain time frame and economic evaluation should be conducted, and label changes or disinvestment should be carried out based on those evaluations.

What Matters for Depression and Anxiety During the COVID-19 Quarantine?: Results of an Online Cross-Sectional Survey in Seoul, South Korea.

Background: Amid the COVID-19 pandemic, quarantine measures are key to containing the spread of the virus. Millions of people have been required to quarantine throughout the pandemic; the quarantine itself is considered detrimental to mental health conditions. Objective: This study aims to investigate the factors associated with depression and anxiety among quarantined people in Seoul, South Korea. Methods: An online cross-sectional survey was administered from October to November 2020 involving people who were living in Seoul, aged 19 years or above, under a 2-week mandatory quarantine. Their mental health status was measured using the Patient Health Questionnares-9 (PHQ-9) and the General Anxiety Disorder-7 (GAD-7). Results: Overall, 1,135 respondents were finally included, resulting in a 22.0% response rate. After controlling for potential confounders, variables, such as the "second half of quarantine period" (OR = 1.78 95% CI: 1.10-2.88), "female" (OR = 1.91 95% CI: 1.16-3.16), and "having pre-existing depression" (OR = 8.03 95% CI: 2.96-21.78) were significantly associated with depression while being quarantined. Those with correct knowledge about the rationale behind for the quarantine (OR = 0.39 95% CI: 0.21-0.72), an understanding of quarantine rules (OR = 0.68 95%CI: 0.52-0.91), and those who felt supported by others (OR = 0.74 95% CI: 0.55-0.99) were less likely to develop depression while quarantining. Similarly, anxiety was significantly associated with the second week (OR = 4.18 95% CI: 1.44-12.09), those with an unstable job status (OR = 3.95 95% CI: 1.60-9.79), perceived support (OR = 0.66, 95% CI: 0.45-0.96), and the fear of being infected (OR = 7.22 95% CI: 1.04-49.95). Conclusions: This study highlights the need to develop precautionary measures to prevent depression and anxiety among people undergoing COVID-19 quarantine. In particular, individuals with depression prior to quarantine should be carefully monitored during the quarantine. Further studies with larger populations are needed.

Pregnancy and Neonatal Outcomes After Exposure to Alprazolam in Pregnancy.

Alprazolam is a commonly prescribed benzodiazepine for anxiety or panic disorder, even in pregnant women. Information on the safety of alprazolam during pregnancy is insufficient. We aimed to evaluate pregnancy and neonatal outcomes after exposure to alprazolam during pregnancy. A prospective study was conducted on 725 pregnancies from January 2000 to December 2019. Participants were recruited through the Korean Mother-Safe Program, a service providing information on drug-induced teratogenic risk during pregnancy and breastfeeding. Exposed (N = 96) and non-exposed (N = 629) women to alprazolam during pregnancy were selected and followed-up until delivery. Pregnancy outcomes, including spontaneous abortion, still birth, low birth weight (LBW), preterm birth, Apgar score (at 1 and 5 min), and malformations were measured and compared. Multivariable logistic regression was performed to examine the association between alprazolam exposure and outcomes. The mean age was 32.9 (SD 4.0) years in the alprazolam-exposed group and 31.8 (SD 3.8) years in the unexposed group (p = 0.008). The alprazolam exposure group demonstrated a significantly higher likelihood of pregnancy and neonatal outcomes: spontaneous abortion (OR = 2.38; 95% CI 1.20-4.69), LBW (OR = 3.65; 95% CI 1.22-11.00), and Apgar score at 1 min ≤ 7 (OR = 2.19; 95% CI 1.02-4.67). There was no significant difference in congenital abnormalities between the exposure and non-exposure groups. Our findings confirmed that alprazolam exposure during pregnancy was significantly associated with adverse pregnancy and neonatal outcomes, including spontaneous abortion, low birth weight, and Apgar score at 1 min ≤ 7. Alprazolam during pregnancy should be appropriately regulated and monitored.

Dissipation and Residue Pattern of Dinotefuran, Fluazinam, Indoxacarb, and Thiacloprid in Fresh and Processed Persimmon Using LC-MS/MS.

Pesticides which are diluted and sprayed according to the pre-harvest interval (PHI) are generally decomposed and lost through various factors and pathways, and the leftover pesticides are known as residual pesticides. This study aims to determine the dissipation of residual amounts of dinotefuran, fluazinam, indoxacarb, and thiacloprid in persimmon and the changes in the concentration of various processing products. Pesticide spraying is performed in accordance with the GAP (good agricultue practice) of Korea, and the processed products are manufactured using a conventional method after removing the skin of persimmons. The modified QuEchERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method and an optimized method using LC-MS/MS (liquid chromatography mass spectrometry) is implemented to analyze the residual pesticides. The linearity, recovery, and LOQ (limit of quantitation) are presented to verify the analysis method. The amount of residual pesticides tested decreases significantly in a time-dependent manner, regardless of the minimal dilution effect present due to growth. The residual concentration does not vary significantly during the processing stage despite the removal of the systemic pesticides, dinotefuran and thiacloprid. The residues of non-systemic pesticides, fluazinam and indoxacarb, are typically removed by the peeling removal and processing methods. The reduction factor of dinotefuran, whose residual concentration is increased, is less than 1, and the absolute amount of pesticides is decreased through processing. The results of this study can be used as the scientific basis data to ensure the safety of residual pesticides in processed products in the future.

Corrigendum: Pregnancy and Neonatal Outcomes After Exposure to Alprazolam in Pregnancy.

[This corrects the article DOI: 10.3389/fphar.2022.854562.].

Application of the Health Technology Assessment in Korean Traditional Medicines.

Background: South Korea is the first Asian country to adopt health technology assessment (HTA) as a tool to support decision-making concerning pricing and reimbursement of drugs in 2007. Korean traditional medicines have been continuously marginalized in the modern paradigm of evidence-based medicine. To nurture Korean medicines, clinical practice guidelines for Korean medicines have been developed through government-led initiatives, and HTAs have been applied for the National Health Insurance coverage of Korean medicines. In this study, 27 diseases were selected for analyzing the evidence development of both clinical and economic values of Korean medicines. Methods: To investigate the status quo in application of HTA in Korean medicines, reports on the cost-effectiveness analysis project comprising 27 Korean medical interventions were reviewed. Results: All the selected studies were trial-based economic appraisals and their effectiveness was estimated with a subjective judgment tool, such as the quality of life measurement or visual analog scale. This study reconfirmed the limitations of Korean medicines, which included a short observation period, nonrandomized controlled trials, small sample size, subjective assessment for efficacy, selection bias, large uncertainty, and lack of evidence. Conclusions: Priorities should be placed on establishing the clinical evidence of Korean medicines, which will serve as the base for expanding the health coverage of Korean medicines and improving satisfaction and reliability of oriental medicines in Korea's health care system. Furthermore, the need to nurture the institutional environment in which both oriental and Western medicines can collaborate in Korea should be emphasized.

Depression During COVID-19 Quarantine in South Korea: A Propensity Score-Matched Analysis.

BACKGROUND: Quarantine, a public health measure used to control the coronavirus disease 2019 (COVID-19) pandemic, has been linked to an increased risk of developing adverse psychological sequelae. This study sought to investigate whether quarantining during the COVID-19 pandemic was associated with depression among Koreans. METHODS: Data were obtained from the Seoul COVID-19 Study of Quarantine (SCS-Q) and the 2019 Korea Community Health Survey (KCHS). Using propensity scores estimated based on sociodemographic and health conditions, 919 individuals undergoing quarantine in the SCS-Q were matched with 919 individuals who did not experience quarantine in the 2019 KCHS. Depressive symptoms were measured using the Korean version of the Patient Health Questionnaire-9 (PHQ-9), where major depression is defined as a PHQ-9 score ≥ 10. Logistic regression models were adjusted for sociodemographic and health-related factors. RESULTS: Depression prevalence was higher in quarantined individuals than in the control group (7.8 vs. 3.8%, p < 0.001). Logistic regression analyses revealed that quarantining was associated with higher likelihoods of having major depression [odds ratio (OR) = 2.28, 95% confidence interval (CI): 1.49, 3.51] after adjusting for relevant covariates. LIMITATIONS: Due to the online nature of the SCS-Q, this study included a limited number of elderly participants, limiting the generalizability of the findings to the general Korean population. CONCLUSIONS: The findings suggest that Koreans undergoing COVID-19 quarantine are at higher risk of depression. While further investigation is warranted, public health measures to control infectious disease outbreaks, such as quarantine, would benefit from incorporating strategies to address unintended adverse psychological effects, such as depression.

Evidence-based public policy making for medicines across countries: findings and implications for the future.

Aim: Global expenditure on medicines is rising up to 6% per year driven by increasing prevalence of non-communicable diseases (NCDs) and new premium priced medicines for cancer, orphan diseases and other complex areas. This is difficult to sustain without reforms. Methods: Extensive narrative review of published papers and contextualizing the findings to provide future guidance. Results: New models are being introduced to improve the managed entry of new medicines including managed entry agreements, fair pricing approaches and monitoring prescribing against agreed guidance. Multiple measures have also successfully been introduced to improve the prescribing of established medicines. This includes encouraging greater prescribing of generics and biosimilars versus originators and patented medicines in a class to conserve resources without compromising care. In addition, reducing inappropriate antibiotic utilization. Typically, multiple measures are the most effective. Conclusion: Multiple measures will be needed to attain and retain universal healthcare.

Current utilization patterns for long-acting insulin analogues including biosimilars among selected Asian countries and the implications for the future.

INTRODUCTION: Prevalence rates for diabetes mellitus continue to rise, which, coupled with increasing costs of complications, has appreciably increased expenditure in recent years. Poor glycaemic control including hypoglycaemia enhances complication rates and associated morbidity, mortality and costs. Consequently, this needs to be addressed. Whilst the majority of patients with diabetes have type-2 diabetes, a considerable number of patients with diabetes require insulin to help control their diabetes. Long-acting insulin analogues were developed to reduce hypoglycaemia associated with insulin and help improve adherence, which can be a concern. However, their considerably higher costs have impacted on their funding and use, especially in countries with affordability issues. Biosimilars can help reduce the costs of long-acting insulin analogues thereby increasing available choices. However, the availability and use of long-acting insulin analogues can be affected by limited price reductions versus originators and limited demand-side initiatives to encourage their use. Consequently, we wanted to assess current utilisation rates for long-acting insulin analogues, especially biosimilars, and the rationale for patterns seen, across multiple Asian countries ranging from Japan (high-income) to Pakistan (lower-income) to inform future strategies. METHODOLOGY: Multiple approaches including assessing utilization and prices of insulins including biosimilars among six Asian countries and comparing the findings especially with other middle-income countries. RESULTS: Typically, there was increasing use of long-acting insulin analogues among the selected Asian countries. This was especially the case enhanced by biosimilars in Bangladesh, India, and Malaysia reflecting their perceived benefits. However, there was limited use in Pakistan due to issues of affordability similar to a number of African countries. The high use of biosimilars in Bangladesh, India and Malaysia was helped by issues of affordability and local production. The limited use of biosimilars in Japan and Korea reflects limited price reductions and demand-side initiatives similar to a number of European countries. CONCLUSIONS: Increasing use of long-acting insulin analogues across countries is welcomed, adding to the range of insulins available, which increasingly includes biosimilars. A number of activities are needed to enhance the use of long-acting insulin analogue biosimilars in Japan, Korea and Pakistan.

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.