Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population.

BACKGROUND: Recently, active surveillance (AS) has been introduced as an alternative to early surgery (ES) for the management of papillary thyroid microcarcinoma (PTMC), because of its indolent features and low mortality. However, its cost effects have not been determined and the findings of current studies differ, according to each country's medical system. METHODS: A Markov model was constructed to compare the cost-effectiveness of AS and ES, based on a reference case of a 40-year-old patient diagnosed with PTMC. Costs and transition probabilities were derived from previous clinical studies in Korean populations, and the incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were calculated. The willingness-to-pay (WTP) threshold was set at USD 100,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address the uncertainties in the model's variables. RESULTS: From the base scenario, the cumulative costs and effectiveness were both higher in ES than AS. The ICER for ES, compared with AS, was USD 6,619.86/QALY, lower than the set WTP. The NMB difference between AS and ES increased across the stages (USD 5,980 at the first stage and USD 159,667 at the last stage). The ICER increased along with decreasing age and increasing cost of surgery. The higher the ES utility score and the lower that of AS, the more cost-effective ES, with WTP set at USD 30,000. CONCLUSION: In the current Korean medical system, ES is more cost-effective than AS. ES is more cost-effective as it is diagnosed at young age and followed-up for a long time.

Relationship between screen time among children and lower economic status during elementary school closures due to the coronavirus disease 2019 pandemic.

BACKGROUND: This study aimed to examine whether the extended use of a variety of digital screen devices was associated with lower economic status and other environmental factors among Korean elementary school children and their caregivers during school closures precipitated by the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A total of 217 caregivers of children 7-12 years of age from Suwon, Korea, were recruited and asked to respond to a self-administered questionnaire in June 2020. The questionnaire addressed demographic information and children's use of digital media, in addition to their caregivers. The t-test was used for continuous variables, and the Kruskal-Wallis test was used for variables measured on an interval scale. A multiple regression analyses were performed to examine the effects of significant correlative factors on screen time in children as predictors. RESULTS: Children with lower household incomes demonstrated a higher frequency and longer duration of smartphone and tablet personal computer use compared to those from higher income households. Children of households in which incomes decreased after COVID-19 used smartphones and tablet PCs more often and for longer durations. Children from households that experienced decreased income(s) after COVID-19 used personal computers more often and for a longer duration, and children from low-income families engaged in longer screen time on smartphones. A change in primary caregiver(s) may have increased children's screen time on smartphones. CONCLUSION: Lower household income was associated with longer screen time among children, and poor mental health among caregivers during school closures precipitated the COVID-19 pandemic.

Maternal Depression and Children's Screen Overuse.

BACKGROUND: It is known that there are various factors associated with children's screen overuse. The aim of this study was to examine the effect of maternal depression on 2-5-year-old children's overuse of various household screen devices. METHODS: Participants were from the Internet-Cohort for Understanding of internet addiction Risk factors/Rescue in Early livelihood (I-CURE) study, an observational prospective cohort study in Korea. Screen time for six types of screen devices (smartphone, television, computer, tablet, video gaming console, and portable gaming console) were assessed by parental questionnaire. Maternal depression was measured by the Korean version of the Beck Depression Inventory II. Logistic regression models were run to determine the association between maternal depression and children's screen overuse. RESULTS: Maternal depression was associated with children's television overuse after adjusting for other factors (odds ratio, 1.954; P = 0.034). Contrary to expectation, the relationship between maternal depression and screen time was not present on other devices such as smartphones, computers and tablets. CONCLUSION: Maternal depression is related with 2-5-year-old children's television overuse. Interventions in maternal depressive symptoms and the associated changes in parent-child relationship can be useful for preventing children's television overuse.

Cost-Utility Analysis of Early Detection with Ultrasonography of Differentiated Thyroid Cancer: A Retrospective Study on a Korean Population.

BACKGRUOUND: There is debate about ultrasonography screening for thyroid cancer and its cost-effectiveness. This study aimed to evaluate the cost-effectiveness of early screening (ES) versus symptomatic detection (SD) for differentiated thyroid cancer (DTC) in Korea. METHODS: A Markov decision analysis model was constructed to compare the cost-effectiveness of ES and SD. The model considered direct medical costs, health outcomes, and different diagnostic and treatment pathways. Input data were derived from literature and Korean population studies. Incremental cost-effectiveness ratio (ICER) was calculated. Willingness-to-pay (WTP) threshold was set at USD 100,000 or 20,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address uncertainties of the model's variables. RESULTS: In a base case scenario with 50 years of follow-up, ES was found to be cost-effective compared to SD, with an ICER of $2,852 per QALY. With WTP set at $100,000, in the case with follow-up less than 10 years, the SD was cost-effective. Sensitivity analysis showed that variables such as lobectomy probability, age, mortality, and utility scores significantly influenced the ICER. Despite variations in costs and other factors, all ICER values remained below the WTP threshold. CONCLUSION: Findings of this study indicate that ES is a cost-effective strategy for DTC screening in the Korean medical system. Early detection and subsequent lobectomy contribute to the cost-effectiveness of ES, while SD at an advanced stage makes ES more cost-effective. Expected follow-up duration should be considered to determine an optimal strategy for DTC screening.

An Industry Survey on Unmet Needs in South Korea's New Drug Listing System.

INTRODUCTION: Since introducing the positive listing system in 2007, the South Korean government has undergone multiple changes in its drug listing system. As there is a lack of studies that evaluate the system from an industry perspective, this paper examined South Korea's new drug listing system from the suppliers' perspective. METHODS: We surveyed members of the three main pharmaceutical industry associations online. The survey (a 5-point Likert scale) covered their satisfactory levels, demands, and updates on the current new drug listing system, especially pharmacoeconomic evaluation, pharmacoeconomic evaluation exemption, and risk-sharing agreement. RESULTS: A total of 56 respondents participated in the survey. The self-reported satisfaction level for value recognition of new drugs was 1.6 (± 0.7) points (5 points = very satisfied). The most highly demanded reforms for PE, RSA, and PEE were incremental cost-effectiveness ratio threshold (92.9%), reimbursement scope expansion (91.1%), and eligible disease (83.9%). Lastly, they also claimed that the indication-based pricing system must be introduced (83.9%). CONCLUSIONS: Pricing and reimbursement policies need to improve in such a way that would enable better access to new drugs while still facilitating their development. Given the nature of the current system, some innovative rare disease treatments and anticancer drugs remain unreimbursed, resulting in low satisfaction levels across the pharmaceutical industry. Hence, pathways to speed up the reimbursement assessment process and expand the range of reimbursable diseases are required. Pharmaceutical companies are also important stakeholders, like in the case of clinicians and patients, and their opinions should also be considered in the process of pricing and reimbursement policy reforms.

Effects of Frequent Smartphone Use on Sleep Problems in Children under 7 Years of Age in Korea: A 4-Year Longitudinal Study.

The use of electronic screen devices has a negative effect on sleep. The purpose of this study is to longitudinally examine the effects of various screen use on sleep problems in children under 7 years of age. A total of 314 caregivers of children aged 4−7 years from three cities in Korea were recruited and responded to a self-administered questionnaire from 2017 to 2020. As a result of the analysis of the mixed model designed as a two-leveled structure, the use frequency of smartphones significantly predicted children's sleep problems (ß = 0.328, p < 0.001) compared to that of TV, PC, and tablet PC. In addition, the frequency of smartphone screen use showed a weak but significant correlation with bedtime resistance (r = 0.067, p = 0.009), sleep duration (r = 0.089, p <0.001), nighttime awakening (r = 0.066, p = 0.010), and daytime sleepiness (r = 0.102, p < 0.001). The results of this study suggest that screen time education in Korea should focus on smartphones above all else.

The current state of patient access to new drugs in South Korea under the positive list system: evaluation of the changes since the new review pathways.

Objective: This study aims to provide an up-to-date analysis of the current state of patient access to new drugs in South Korea, focusing on the effect of new review pathways for reimbursement. Methods: We analyzed patients' access to new drugs, listing rate and lead time until listing from marketing authorization. New pathways were defined as 'price negotiation waiver,' 'risk-sharing agreements,' and 'pharmacoeconomic evaluation exemption.' Results: The listing rate for drugs increased after the introduction of the new pathways (93.7% vs. 77.9%, p < 0.001). Before the new pathways, the median lead time for listing was 21.0 months (95% CI: 16.9-25.0), while afterward it was shortened to 10.9 months (95% CI: 10.2-11.7) (p < 0.001). Conclusion: Although it has strengthened national health insurance coverage by positively impacting the rate and lead time, the lead time for the oncology and orphan drugs is substantially longer as compared to other drugs. Expanding the eligibility criteria to include non-life-threatening but rare or intractable diseases, and resolving the system's operational issues are still necessary.

Trends in the pricing and reimbursement of new anticancer drugs in South Korea: an analysis of listed anticancer drugs during the past three years.

Objective: This study aimed to examine patient accessibility to new anticancer drugs including reimbursement coverage, time to listing, and listing price during the recent 3 years after the introduction of alternative pricing and reimbursement pathways in South Korea.Methods: Anticancer drugs were selected for analysis from the new drugs reviewed from January 2017 to March 2020. Descriptive statistics were used to present the levels of the listing prices. Pearson's correlation analysis was used to analyze the relationship between the list price in comparison to the External Reference Price(ERP) and the time to listing.Results: Thirty-two anticancer drugs were included in analysis. The average time to listing for these drugs was 36.7 months. The ratio of the listing price in comparison with Average Adjusted Price from seven reference countries was from 12.6% to 90.2%. Pearson's correlation coefficient for the correlation between the ratio of the listing price to the ERP and the time to listing was -0.37 and was statistically significant (p = 0.035).Conclusions: Policies that relate to the scope of reimbursement, time to reimbursement, and list price should be able to equally reflect patient accessibility and national health insurance finances, as well as the impact on industry as a whole.

Price-Cutting Trends in New Drugs after Listing in South Korea: The Effect of the Reimbursement Review Pathway on Price Reduction.

This study aims to analyze the trends of post-listing price changes for new drugs listed from 2007, when the health technology assessment (HTA) was introduced in South Korea, until 2017. We analyzed 135 products that have undergone price cuts. These products were analyzed by their respective review pathways, namely, pharmaco-economic study (PE), weighted average price (WAP), and the without a cost-effectiveness (CE) pathway. Prices were discounted faster in PE than in WAP (p = 0.002 in a comparison between PE and WAP). In addition, the median discount rate of the first price cut was 5.0% (range: 0.1-20.0) for PE, 3.0% (range: <0.1-30.0) for WAP, and 5.0% (range: 0.6-10.9) without a CE pathway. The median cumulative discount rate of PE and WAP showed that the PE pathway products' discount rates were higher: 10.4% for PE and 6.0% for WAP (p = 0.025 for comparison between PE and WAP). It is necessary to discuss the practical effects of the price-cutting system from a myriad of perspectives, including insurance finance, the value of new drugs, and the accessibility of new drugs to patients.

Cost-Utility Analysis of Sacubitril/Valsartan Use Compared With Standard Care in Chronic Heart Failure Patients With Reduced Ejection Fraction in South Korea.

PURPOSE: Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is a possible treatment option for chronic heart failure patients with reduced ejection fraction (HFrEF). The aim of this study was to estimate the cost-effectiveness of sacubitril/valsartan use in South Korea for treating patients with HFrEF compared with that of enalapril, an angiotensin-converting enzyme inhibitor, and with angiotensin receptor blockers (ARBs). METHODS: A Markov model was designed to estimate the lifetime cost-effectiveness of treatment for patients with HFrEF. Cohorts in the alive-state incurred a monthly risk of hospitalization because of deteriorated HF, adverse events (AEs), or death. Transition probabilities of sacubitril/valsartan and enalapril were estimated by using data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. The effectiveness of ARBs (eg, reduction in mortality and hospitalization rates) was assumed to be identical to that of enalapril, according to the results of the meta-analysis. However, there was no comparative evidence for AEs. We therefore conducted a Bayesian network meta-analysis and adjusted the incidence rate of AEs for ARBs. The utility for estimating quality-adjusted life years (QALYs) was elicited by the survey of the general South Korean population by using EuroQol-5 dimensions. We calculated the medical costs, including medication, monitoring, hospitalization, AEs, and terminal care, from the health care sector perspective. Costs and effectiveness were discounted by 5%. One-way sensitivity analyses and a probabilistic sensitivity analysis were conducted to determine the model robustness. FINDINGS: The total cost per patient for sacubitril/valsartan and enalapril was $25,832 and $18,295, respectively. Sacubitril/valsartan was associated with an ∼8- month longer life expectancy compared with enalapril and a QALY gain of 0.59. As a result, the incremental cost-effectiveness ratio for sacubitril/valsartan versus enalapril was $12,722 per QALY. The incremental cost-effectiveness ratio of sacubitril/valsartan versus ARB was $11,970 with an incurred cost of $18,741 for the ARB group. The main results and those of various sensitivity analyses were lower than a threshold of $20,000. IMPLICATIONS: From a health care sector perspective, sacubitril/valsartan is a cost-effective treatment for HFrEF compared with enalapril and ARBs. This finding could be helpful for cardiologists or decision makers in reaching cost-effective choices regarding the treatment selection process.

Reference values of hematology, biochemistry, and blood type in cynomolgus monkeys from cambodia origin.

Cynomolgus monkeys as nonhuman primates are valuable animal models because they have a high level of human gene homology. There are many reference values for hematology and biochemistry of Cynomolgus monkeys that are needed for proper clinical diagnosis and biomedical research conduct. The body weight information and blood type are also key success factors in allogeneic or xenogeneic models. Moreover, the biological parameters could be different according to the origin of the Cynomolgus monkey. However, there are limited references provided, especially of Cambodia origin. In this study, we measured average body weight of 2,518 Cynomolgus monkeys and analyzed hematology and serum biochemistry using 119 males, and determined blood types in 642 monkeys with Cambodia origin. The average body weight of male Cynomolgus monkeys were 2.56±0.345 kg and female group was 2.43±0.330 kg at the age from 2 to 3 years. The male group showed relatively sharp increased average body weight from the 3 to 4 age period compared to the female group. In hematology and biochemistry, it was found that most of the data was similar when compared to other references even though some results showed differences. The ABO blood type result showed that type A, B, AB, and O was approximately 15.6, 33.3, 44.2, and 6.9%, respectively. The main blood type in this facility was B and AB. These biological background references of Cambodia origin could be used to provide important information to researchers who are using them in their biomedical research.

Post-metastasis survival in extremity soft tissue sarcoma: a recursive partitioning analysis of prognostic factors.

BACKGROUND: Recursive partitioning analysis (RPA) enables grouping of patients into homogeneous prognostic groups in a visually intuitive form and has the capacity to account for complex interactions among prognostic variables. In this study, we employed RPA to generate a prognostic model for extremity soft tissue sarcoma (STS) patients with metastatic disease. METHODS: A retrospective review was conducted on 135 patients with metastatic STS who had undergone surgical removal of their primary tumours. Patient and tumour variables along with the performance of metastasectomy were analysed for possible prognostic effect on post-metastatic survival. Significant prognostic factors on multivariate analysis were incorporated into RPA to build regression trees for the prediction of post-metastatic survival. RESULTS: RPA identified six terminal nodes based on histological grade, performance of metastasectomy and disease-free interval (DFI). Based on the median survival time of the terminal nodes, four prognostic groups with significantly different post-metastatic survival were generated: (1) group A: low grade/metastasectomy; (2) group B: low grade/no metastasectomy/DFI ⩾ 12 months or high grade/metastasectomy; (3) group C: low grade/no metastasectomy/DFI < 12 months or high grade/no metastasectomy/DFI ⩾ 12 months; and (4) group D: high grade/no metastasectomy/DFI < 12 months. The 3-year survival rates for each group were: group A, 76.1 ± 9.6%; group B, 42.3 ± 10.3%; group C, 18.8 ± 8.0%; and group D, 0.0 ± 0.0%. CONCLUSION: Our prognostic model using RPA successfully divides STS patients with metastasis into groups that can be easily implemented using standard clinical parameters.

Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

PURPOSE: Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare primary hepatic neoplasm (PHN) with features of both hepatocellular and biliary differentiation. We compared the outcome of hepatic resection in patients with HCC-CC, those with hepatocellular carcinoma (HCC), and those with cholangiocarcinoma (ICC). METHODS: Between November 1994 and December 2003, 952 patients underwent hepatic resection for a PHN. RESULTS: The incidence of HCC-CC was 3.5%. Hepatitis B surface antigen was positive in 51.2% of these patients and the HCV antibody was positive in 12.2%. Positive hepatitis serology was more common in the HCC group (66.7%). The prevalence of underlying liver cirrhosis was significantly lower in the ICC group (7.8%) than in the HCC (49%) and HCC-CC (41.5%) groups (P < 0.0001). The median overall survival periods after hepatic resection of HCC-CC, HCC, and ICC were 47.3, 71.7, and 21.5 months, respectively (P < 0.0001). The median disease-free survival (DFS) periods after hepatic resection for HCC-CC, HCC, and ICC were 23.4, 68.2, and 15.5 months, respectively (P < 0.0001). CONCLUSION: Patients with transitional type HCC-CC had significantly poorer survival rates than those with HCC, after hepatic resection. Therefore, a more aggressive treatment modality should be explored to improve the survival rate of these patients.