Evaluation of changes in the clinical benefits of oncology drugs over time following reimbursement using the ASCO-VF and the ESMO-MCBS.

PURPOSE: This study aims to estimate changes in the value of oncology drugs over time from initial data of the reimbursement decisions to subsequent publications in Korea, using two value frameworks. METHODS: We retrieved primary publications assessed for reimbursement between 2007 and July 2021 from the decision documents of Health Insurance Review and Assessment and subsequent publications made available following reimbursement decision from ClinicalTrials.Gov and PubMed databases. Changes in the clinical benefit scores were assessed using the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). A paired t test was performed to test whether there was a difference in the scores between primary and subsequent publications. RESULTS: Of 73 anticancer product/indication pairs, 45 (61.6%) had subsequent publications, of which 62.5% were released within 1 year of reimbursement decision. The mean ESMO-MCBS and ASCO-VF Net Health Benefit scores increased from primary to subsequent publications, although the differences were not significant. The mean ASCO-VF bonus score significantly increased from 15.91 to 19.09 (p = 0.05). The ESMO-MCBS and bonus scores increased by 0.25 and 0.21, respectively, and the bonus score had a greater impact on the ESMO-MCBS score than the preliminary score did. CONCLUSION: The value of drugs demonstrated in subsequent publications varies considerably among oncology drugs, depending on uncertainty associated with the initial evidence and the availability of updated evidence. As decision-making in the face of uncertainty becomes more prevalent, the value frameworks can serve as simple screening tools for re-evaluation in these cases.

A nationwide analysis of the treatment patterns, survival, and medical costs in Korean patients with relapsed or refractory diffuse large B-cell lymphoma.

Background: Approximately one-third of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to treatment or experience relapse after initial therapy. Unfortunately, treatment options for older patients and those who experience relapse or become refractory to hematopoietic stem cell transplantation (HSCT) are limited. This nationwide population-based study aimed to identify treatment patterns, survival times, and treatment costs in patients with relapsed/refractory DLBCL (R/R DLBCL). Materials and methods: Between 2011 and 2020, data on patients with R/R DLBCL were retrieved from the Korean Health Insurance Review & Assessment Service, encompassing the entire population. We identified the treatment patterns for each treatment line using a Sankey diagram and calculated the median time to the subsequent treatment in line. Median overall and progression-free survival times were estimated using the Kaplan-Meier survival curves. Finally, the medical costs incurred during DLBCL treatment were calculated for each treatment line and the costs related to HSCT were summarized at the episode level. Results: A total of 864 patients with R/R DLBCL who received second-line treatment were identified, and a regimen of ifosfamide, carboplatin, and etoposide (ICE) was administered the most. Among them, 353 were refractory or relapsed cases that were treated with third-line treatments. The median times for second-line to third-line, third-line to fourth-line, fourth-line to fifth-line, and fifth-line to sixth-line treatment failures gradually decreased (3.93, 2.86, 1.81, and 1.38 months, respectively). The median overall survival time was 8.90 and 4.73 months following the second-line and third-line treatments, respectively. In the third-line treatment setting, the patients did not show a significant difference in survival time after HSCT. The median medical cost was $39,491 across all treatment lines including the cost of HSCT which was $22,054. Conclusion: The treatment patterns in patients with R/R DLBCL, especially at third-line treatments and thereafter, were complicated, and their prognosis was poor despite the high medical costs. Novel and effective treatment options are expected to improve the prognosis and alleviate the economic burden of patients with R/R DLBCL.

Comparison of partitioned survival modeling with state transition modeling approaches with or without consideration of brain metastasis: a case study of Osimertinib versus pemetrexed-platinum.

BACKGROUND: The partitioned survival model (PSM) and the state transition model (STM) are widely used in cost-effectiveness analyses of anticancer drugs. Using different modeling approaches with or without consideration of brain metastasis, we compared the quality-adjusted life-year (QALY) estimates of Osimertinib and pemetrexed-platinum in advanced non-small cell lung cancer with epidermal growth factor receptor mutations. METHODS: We constructed three economic models using parametric curves fitted to patient-level data from the National Health Insurance Review and Assessment claims database from 2009 to 2020. PSM and 3-health state transition model (3-STM) consist of three health states: progression-free, post-progression, and death. The 5-health state transition model (5-STM) has two additional health states (brain metastasis with continuing initial therapy, and with subsequent therapy). Time-dependent transition probabilities were calculated in the state transition models. The incremental life-year (LY) and QALY between the Osimertinib and pemetrexed-platinum cohorts for each modeling approach were estimated over seven years. RESULTS: The PSM and 3-STM produced similar incremental LY (0.889 and 0.899, respectively) and QALY (0.827 and 0.840, respectively). However, 5-STM, which considered brain metastasis as separate health states, yielded a slightly higher incremental LY (0.910) but lower incremental QALY (0.695) than PSM and 3-STM. CONCLUSIONS: Our findings indicate that incorporating additional health states such as brain metastases into economic models can have a considerable impact on incremental QALY estimates. To ensure appropriate health technology assessment decisions, comparison and justification of different modeling approaches are recommended in the economic evaluation of anticancer drugs.

Cost-effectiveness of improving patients' adherence to tuberculosis treatment in South Korea using discrete event simulation.

BACKGROUND: Poor adherence to tuberculosis (TB) treatment is an obstacle to controlling the disease. The Korean government's national TB control plan includes a program on adherence to TB treatment to manage patients with TB. This study aimed to assess the cost-effectiveness of a national TB program for improving patient adherence. METHODS: A discrete event simulation (DES) model was developed to estimate the costs and quality-adjusted life-years (QALYs) of adherent and non-adherent patients. In this model, we considered treatment completion, loss to follow-up, recurrence, death, and treatment changes from drug-susceptible to multidrug-resistant TB as clinical events. We obtained input parameters such as costs, probability of events, and time distributions for each event from the Korean National Health Insurance claims data. We estimated the costs and QALYs before implementation of the program (adherence rate = 79%) and at present (current adherence rate = 94%). The incremental cost-effectiveness ratio (ICER) was used to evaluate whether the program was cost-effective given the willingness-to-pay threshold. RESULTS: In the simulation, the program increasing the proportion of adherent patients gained 0.018 QALY/patient while spending $162/patient. The ICER of the TB program was $8790/QALY. Given a willingness-to-pay threshold of $20,000, the national TB program was considered cost-effective. CONCLUSION: Improvements in adherence to TB treatment through the current TB program were cost-effective. The DES model accurately reflected the real world. Commitment programs to improve patient adherence may help manage TB nationwide.

Estimating the Total Societal Cost of a Hexavalent Vaccine versus a Pentavalent Vaccine with Hepatitis B in South Korea.

In South Korea, the ready-to-use hexavalent vaccine (against diphtheria, tetanus, pertussis, poliovirus, Haemophilus influenzae type b, and hepatitis B) is not listed despite its facility of no need to reconstitute. It, therefore, has the potential to augment the efficiency of prevention against the six infectious diseases, and it may reduce vaccine-related errors of reconstitution when compared with the currently used vaccination scheme of the pentavalent vaccine with the additional shots against hepatitis B. Given the assumed clinical equivalence between the two vaccination schemes, a cost-minimization analysis has been performed from a societal perspective including all the medical and non-medical direct and indirect costs when vaccinating one birth cohort. The results indicate that the ready-to-use hexavalent vaccine induces a cost reduction of KRW 47,155 (USD36.22) per infant or 12,026 million Korean Won ($9,236,417) in total for the whole birth cohort with 260,500 children. Using the ready-to-use hexavalent vaccine causes a lower infection rate, has fewer vaccination sessions, and may save much time as compared with the current vaccination scheme in place. The ready-to-use hexavalent vaccine may, therefore, benefit the National Immunization Program by reducing the total societal costs of vaccination while improving convenience of infants, parents, and medical care professionals.

Economic Burden of Recurrence in Completely Resected Stage IB-IIIA Non-Small Cell Lung Cancer: A Retrospective Study Using Nationwide Claims Data of South Korea.

INTRODUCTION: Although many patients with early stage non-small cell lung cancer (NSCLC) experience recurrence despite complete resection, few studies have reported on the corresponding economic burden. This study aimed to understand the economic impact of recurrence by measuring healthcare costs and resource utilization in patients with recurrent stage IB-IIIA NSCLC. METHODS: Using Health Insurance Review and Assessment claims data from South Korea, we included patients who underwent complete resection for stage IB-IIIA NSCLC during the index period (January 1, 2012, to October 31, 2018). Patients who experienced recurrence were matched with those who did not using 1:1 propensity score (PS) matching. The mean healthcare costs and resource utilization were analyzed from the date of complete resection to the last claims for cancer treatment. A generalized linear model (GLM) was used to estimate the impact of covariates on healthcare costs. A difference-in-difference (DID) analysis was conducted to analyze the healthcare costs between the two groups before and after recurrence. RESULTS: Patients with recurrence incurred higher healthcare costs, particularly in outpatient settings. The cost of targeted therapy and immune checkpoint inhibitors primarily contributed to cost differences, and medication costs increased over time after complete resection. Patients with recurrence were also hospitalized more frequently (9.3 vs. 5.0, p < 0.0001) for a longer period (74 days vs. 42 days, p < 0.0001) than those without recurrence. GLM analysis showed that the total cost was 2.31-fold higher in patients with recurrence (95% confidence interval: 2.19-2.44). The DID analysis showed significantly increased total costs in patients with recurrence (ß = 26,269, p < 0.0001), which was mostly attributed to medication costs (ß = 17,951, p < 0.0001). CONCLUSION: Recurrence of completely resected NSCLC leads to a substantial increase in healthcare costs and resource utilization. The results of this study show the economic burden of recurrence, which may help future economic analyses and resource allocation.

Quantitative Benefit-Risk Assessment of COVID-19 Vaccines Using the Multi-Criteria Decision Analysis.

In the early SARS-CoV-2 (COVID-19) pandemic, four major vaccines were approved despite limited efficacy and safety data through short regulatory review periods. Thus, it is necessary to assess the benefit-risk (BR) profiles of the COVID-19 vaccines. We conducted a quantitative BR assessment for four COVID-19 vaccines (mRNA-based: mRNA-1273 and BNT162b2; viral vector-based: Ad26.COV.2 and ChAdOx1-S) using multi-criteria decision analysis. Three benefit criteria and two risk criteria were considered: preventing COVID-19 infection for (1) adults aged ≥18 years; (2) seniors aged 60 years or older; and (3) severe COVID-19, adverse events (AEs), and serious AEs. Data were retrieved from clinical trials, observational studies, and county-specific AE monitoring reports. Based on the collected data, vaccines were scored for each criterion. 22 professionals weighted each criterion. The overall BR score was calculated using scores and weights. mRNA-1273 was the most preferred vaccine in pre-authorization and BNT162b2 in post-authorization. We found that the mRNA vaccine had a good balance between the benefits and risks. Using this BR assessment, the benefit-risk profile of COVID-19 vaccines can be updated with cumulated data. It will contribute to building evidence for decision making by policy makers and health professionals.

Clinical impact and economic burden of post-transplant infections following heart transplantation: A retrospective nationwide cohort study.

BACKGROUND: Post-transplant infections are associated with high mortality rates. This retrospective nationwide cohort study examined the incidence and risk factors of infections requiring hospitalization after heart transplantation and the associated economic burden. METHODS: The entire heart transplant recipients' data from the Korean Health Insurance Review and Assessment Service between 2013 and 2020 was used. We estimated the annual incidence of post-transplant infections and adjusted incidence rate ratios (aIRR) of risk factors for reported infections using the poisson generalized linear model. RESULTS: Among 1,030 heart transplant recipients (324 with and 706 without post-transplant infections), 0.45 post-transplant infections were reported annually, with respiratory tract infections constituting the highest proportion (0.16). The risk of post-transplant infections was high in recipients with renal failure (aIRR = 1.35; 95% confidence interval [CI], 1.05-1.75) or nosocomial infection (aIRR = 1.47; 95% CI, 1.15-1.87). Combination regimens, including mammalian target of rapamycin inhibitor (mTORi), did not differ significantly from the standard 3 drug regimen (aIRR = 1.16; 95% CI, 0.80-1.67). The risk of death was higher among recipients with post-transplant infections than in uninfected recipients (adjusted hazard ratio = 4.59; 95% CI, 2.19-9.65). The mean follow-up cost per patient per month was 2-fold higher in recipients with post-transplant infections than in uninfected recipients ($5,096 and $2,532, respectively; p < .001). CONCLUSIONS: mTORi combination, which reportedly maintains renal function, can be considered, as it does not increase the infection risk. Post-transplant infections present clinical and economic burdens, warranting careful observation of at-risk patients.

Economic burden of brain metastases in non-small cell lung cancer patients in South Korea: A retrospective cohort study using nationwide claims data.

Brain metastases (BM) are common in patients with non-small cell lung cancer (NSCLC). However, the pure economic burden of BM is unknown. This study aimed to evaluate the impact of BM on healthcare costs and resource utilization in patients with NSCLC by comparing patients with and without BM. This was a retrospective cohort analysis of South Korean health insurance review and assessment claims data. Patients with stage IIIB or IV NSCLC were identified (March 1, 2013 to February 28, 2018). We compared their two-year and per-patient-per-month (PPPM) healthcare costs and resource utilization with 1:3 propensity score-matched patients without the condition. A generalized linear model was used to estimate the impact of BM and other covariates on healthcare costs. After propensity score matching with the 33 402 newly diagnosed cases of stage IIIB or IV NSCLC, 3435 and 10 305 patients were classified as having or not having BM, respectively. Mean healthcare costs were significantly greater in patients with BM for both the two years (US$ 44 692 vs. US$ 32 230, p < .0001) and PPPM (US$ 3510 vs. US$ 2573, p < .0001). The length of hospital stay was longer in patients with BM (79.15 vs. 69.41 days for two years, p < .0001; 7.69 vs. 6.86 days PPPM, p < .0001), and patients with BM had more outpatient visits (50.61 vs. 46.43 times for two years, p < .0001; 3.64 vs. 3.40 times PPPM costs, p < .0001). The costs of drugs, radiology/radiotherapy, and admission comprised the majority of PPPM costs and were higher in patients with BM. The generalized linear model analysis suggested that patients with BM had significantly increased healthcare costs (by 1.29-fold, 95% confidence interval 1.26-1.32). BM is a significant economic burden for patients with NSCLC. Therefore, it is important to prevent BM in patients with NSCLC to reduce their economic burden.

Understanding patient and physician responses to various cost-sharing programs for prescription drugs in South Korea: A multilevel analysis.

Introduction: Patient and/or physician responses are a pivotal issue in designing rational cost-sharing programs under health insurance systems. Objectives: This study aims to understand patient and/or physician responses to cost-sharing programs designed for prescription drugs in South Korea. Methods: As a framework, we took advantage of a tiered cost-sharing program, including from copayment to coinsurance (threshold 1) and reduced coinsurance (threshold 2). Given the hierarchical structure of prescriptions nested within patients, we utilized a multilevel analysis to assess effects of various cost-sharing programs on patient and/or physician responses using National Health Insurance claims data from 2018. Results: We found that a tiered cost-sharing program was effective in changing the behaviors of patients and/or physicians. Threshold 1 was found to be more effective than threshold 2 in changing their behaviors. At the prescription level, sensitivity to cost-sharing programs was associated with prescribed days of treatment and locations of prescription. In a similar vein, sensitivity to cost-sharing programs was associated with gender and age group of patients. Conclusion: A simplified cost-sharing program with extended intervals should be considered to rationalize cost-sharing programs. Specifically, a cost-sharing program designed for long-term prescriptions for chronic diseases together with an emphasis on cost transparency is required to better guide price-conscious decisions by patients and/or physicians.

Clinical manifestation, economic burden, and mortality in patients with transthyretin cardiac amyloidosis.

BACKGROUND: Transthyretin cardiac amyloidosis, also known as transthyretin cardiomyopathy (ATTR-CM) is a poorly-recognized disease with delayed diagnosis and poor prognosis. This nationwide population-based study aimed to identify disease manifestations, economic burden, and mortality of patients with ATTR-CM. METHODS: Data of newly diagnosed patients with ATTR-CM between 2013 and 2018 from the Korean National Health Insurance Service were used, covering the entire population. Patient characteristics included comorbidities, medical procedures, and medication. Healthcare resource utilization and medical costs were observed as measures of the economic burden. The Kaplan-Meier survival curve and years of potential life lost (YPLL) from the general population were estimated for disease burden with ATTR CM. RESULTS: A total of 175 newly diagnosed patients with ATTR-CM were identified. The most common cardiac manifestation was hypertension (51.3%), while the most common non-cardiac manifestation was musculoskeletal disease (68.0%). Mean medical costs at the post-cohort entry date were significantly higher than those at the pre-cohort entry date ($1,864 vs. $400 per patient per month (PPPM), p < 0.001). Of the total medical costs during the study period, the proportion of inpatients cost was 12.9 times higher than the outpatients cost ($1,730 and $134 PPPM, respectively). The median survival time was 3.53 years from the first diagnosis of ATTR-CM, and the mean (SD) YPLL was 13.0 (7.7). CONCLUSIONS: Patients with ATTR-CM had short survival and high medical costs. To reduce the clinical and economic burdens, carefully examining manifestations of disease in patients can help with early diagnosis and treatment.

Cost-Effectiveness Analysis of Smoking Cessation Interventions With Behavioral Support: A Study Based on the Benefits of Smoking Cessation on Outcomes (BENESCO) Model.

INTRODUCTION: Few studies have compared cost-effectiveness of different smoking cessation interventions (SCIs) that include behavioral support, considering smoking-related diseases. Therefore, we compare the cost-effectiveness of SCIs with behavioral support in South Korea using the Benefits of Smoking Cessation on Outcomes (BENESCO) model. AIMS AND METHODS: We used the BENESCO model to estimate the cost and utility of the SCIs with behavioral support, including pharmacist counseling with nicotine replacement therapy (pharmacist+NRT), expert counseling with NRT (expert+NRT), and expert counseling with varenicline (expert+varenicline). The target population was adult smokers who wanted to cease smoking within 1 month. We applied transitional probabilities and epidemiological data from the literature. Medical costs and utilities were calculated using claims and national survey data, respectively. Cost-effectiveness was evaluated within the threshold (17 926 USD per quality-adjusted life years [QALYs]) by incremental cost-effectiveness ratio (ICER). RESULTS: The model cohort included 1 219 390 male and 298 511 female smokers. The pharmacist+NRT group had 32 842 more QALYs gained and 26 689 958 USD less expended than the expert+NRT group. The ICER for the expert+varenicline group versus the pharmacist+NRT and expert+NRT groups was 27 247 and 4074 USD per QALY, respectively. The robustness of the results was confirmed by sensitivity analyses, except for the discount rate and cost of the expert+varenicline group. CONCLUSIONS: In Korea, pharmacist counseling with NRT showed higher QALY gains and lower costs than expert counseling with NRT. Expert counseling with varenicline was more effective for smoking cessation and more cost-effective than expert counseling with NRT but was not cost-effective compared with pharmacist counseling with NRT. IMPLICATIONS: This study provides evidence for decision-making on smoking cessation programs by evaluating the cost-effectiveness of SCIs. Furthermore, we attempted to use the BENESCO model to compare and evaluate the cost-effectiveness of SCIs with behavioral support. It is meaningful because this study showed the availability of using the BENESCO model in the future cost-effectiveness analysis of various SCIs.

Healthcare resource utilization and medical costs in patients with terminal cancer during best supportive care.

Patients with terminal cancer have different physical symptoms, prognoses, emotional distress, and end-of-life care plans from those receiving aggressive chemotherapy; few studies have assessed healthcare resource use in these patients. Therefore, this study aimed to assess healthcare resource utilization and medical costs incurred during best supportive care after the last anticancer drug treatment in patients with terminal cancer. This retrospective observational study was conducted using national sample cohort data from the National Health Insurance Service in South Korea. Only patients with cancer who were treated with the last anticancer drugs from January 1, 2006, to June 30, 2015, were included in the study. The period of best supportive care was defined as the time from the date of use of the last anticancer drug to death. Healthcare resource utilization and medical costs were estimated during the best supportive care. A generalized linear model with a log-link function and gamma distribution was used to evaluate the impact of demographic and healthcare utilization factors on total medical costs. Among the 2,480 patients in the study, 93.9% were hospitalized, and hospitalization days (30.8 days) accounted for 39.7% of the surviving period (77.5 days). The proportions of intensive care unit admissions and emergency department visits were 15.8% and 18.9%, respectively. The average total medical cost per patient was $6,310, with the inpatient cost ($5,705) being approximately 9.4 times higher than the outpatient cost ($605). The length of hospitalization had the greatest impact on the total medical costs. Pancreatic cancer had the highest proportion of patients who were hospitalized (97.4%) and the highest medical cost ($7,702). Hospital-based resources were utilized by most patients with terminal cancer, and hospitalization was a major driver of the total medical cost. An alternative system for hospitalization should be developed to support patients with terminal cancer, both clinically and financially.

Value-Based Pricing and Budget Impact Analysis for Multi-Indication Drugs: A Case Study of Immunotherapies.

We aimed to calculate the value-based price of each indication and compare the drug price and budget impact among value-based pricing (VBP) scenarios, using immunotherapy as a case. Atezolizumab, nivolumab, and pembrolizumab prices were estimated for VBP scenarios, namely indication value-based pricing (IBP), IBP with refund, and weighted-average pricing (WAP). To estimate the value-based price of each indication, cost-effectiveness analyses were conducted by setting the incremental cost-effectiveness ratio of the first reimbursed indication to the threshold. The budget impact for each scenario was compared with that of the pricing system in Korea (which has a 4.75% price reduction). The value-based prices of non-reimbursed indications were lower for atezolizumab and higher for nivolumab than those for the reimbursed indication. The drug price fluctuations were the largest in IBP, varying between 28.56-328.81% of the current list price. The net price of the non-reimbursed indications decreased from 0% to 71.44% in IBP with refund, and the budget impact was the lowest among VBPs. Although the fluctuation in the budget impact in WAP was smaller than IBP, higher drug prices were identified for low-value indications. In conclusion, IBP with refund is a viable method for multi-indication drugs, because it has minimal drug price and budget impact changes.

Importance of a usual source of care in choosing low-priced generic drugs: a cross-sectional study.

BACKGROUND: The potential to lower pharmaceutical spending exists if physicians prescribe low-priced generics. This study aimed to empirically investigate the determinants of choosing low-priced generic drugs in South Korea. METHODS: The 2018 HIRA-NPS dataset was used for this study. Among 1.45 million individuals, we identified the patients who were prescribed atorvastatin 10 mg for more than 60 days in 2018 as the study subjects, separated the subjects into high- and low-priced groups based on their average unit price, and applied a series of logistic regression models to elucidate the factors affecting low-priced drug choice. RESULTS: Out of 60,984 subjects, only 10,228 (17%) were categorized into the low-priced group. The majority of the subjects (31%) were prescribed drugs at the maximum reimbursement price. Age of the subject, the frequency of visits to the institution, the existence of a usual source of care, and the institution type that a subject mainly visited for prescriptions were associated with being prescribed low-priced generics. CONCLUSION: The association of being prescribed low-priced generics with the primary care institution and the usual source of care could be interpreted as evidence for the role of primary care in the continuity of patient-centred care. Creating health systems under which professionals act as perfect agents of a patient and/or an insurer is required.

Generic drugs with a discounted price compared to their corresponding brand-name drugs could be prescribed for patients. Therefore, spending on pharmaceuticals could be saved if physicians prescribed low-priced generics and/or patients switched from high-priced drugs to low-priced drugs. Policymakers have introduced several ways to encourage choosing low-priced generic drugs. This study focussed on the factors associated with choosing low-priced generic drugs in South Korea. Contrary to our expectations, only a few patients (17% of the total patients) choose low-priced generics, indicating potential to save pharmaceutical expenditure. Geriatric patients, patients who mainly visited primary healthcare institutions, and patients who had a usual source of care were more likely to choose low-priced generics. This study also suggested various ways to encourage choosing low-priced generic drugs in health systems.

Cost-Effectiveness of Adjuvant Immunotherapy With Cytokine-Induced Killer Cell for Hepatocellular Carcinoma Based on a Randomized Controlled Trial and Real-World Data.

BACKGROUND: Studies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain. METHODS: We constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses. RESULTS: Based on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER. CONCLUSION: We showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice.

A Systematic Review of Economic Evaluations of Active Tuberculosis Treatments.

Background: The disease burden of active tuberculosis (TB) is considerable, but systematic reviews of economic evaluations of active TB treatments are scarce. Methods: PubMed, EMBASE, and the Cochrane Library databases were used to search for articles on cost-effectiveness analysis or cost-utility analysis that economically evaluated active TB treatments, which were then systematically reviewed by two independent reviewers. We extracted vital components of the included studies, such as country, population, intervention/comparator, primary outcome, values of outcomes, thresholds, model type, time horizon, and health states included in the model. Results: Seventeen studies were included in this systematic review. Thirteen dealt with interventions of medications, and the remaining four compared care strategies. The Markov model was the most commonly used tool to compare medications, whereas studies on care plans mainly used decision trees. The most commonly used primary outcome was disability-adjusted life years, followed by quality-adjusted life years. For treatment-naïve TB, the 4-month regimen was more cost-effective than the 6-month regimen mainly in low- and middle-income countries. For multidrug-resistant TB, a bedaquiline-based regimen was cost-effective. For multidrug-resistant TB, decentralized care that employed the use of home or mobile devices was more cost-effective than hospital-based centralized care in low- and middle-income countries. Conclusion: New treatment strategies to improve therapeutic outcomes by enhancing treatment adherence, such as regimens with shorter durations (2 or 4 months) and decentralized care, or new anti-TB agents (e.g., bedaquiline) have been suggested as cost-effective interventions for active TB. This review provides information on the economic evaluation of active TB from good-quality studies, thus aiding the future economic evaluation of active TB.

Real-world data analysis of the clinical and economic burden and risk factors in patients with major depressive disorder with an inadequate response to initial antidepressants.

AIM: We aimed to determine the incidence of and identify the factors associated with treatment-resistant depression (TRD), psychiatric conditions, hospitalization, and cost in patients with major depressive disorder (MDD) who were treated using second-line strategies after an inadequate response to initial antidepressants (AD). MATERIALS AND METHODS: Using South Korean National Health Insurance claims data (1 January 2013 to 30 June 2018), we conducted a retrospective cohort analysis in newly treated patients with MDD who subsequently switched or added AD, or added atypical antipsychotics (AAPs) as a second-line treatment. We assessed the incidence of treatment-resistant depression (TRD), psychiatric conditions, and hospitalization for the first 2 years and costs in the third year. Odds ratios (ORs) or relative ratios were estimated using logistic and linear regression models to identify the risk factors for clinical and economic outcomes. RESULTS: In 15,887 patients, the TRD was 16.81% during the 24-month follow-up period (14.14% in switching AD, 19.65% in adding AD, and 19.91% in adding AAP; p < 0.0001). When adding AD or AAP, the OR of TRD was 1.43 (95% confidence interval (CI): 1.30-1.56) and 1.42 (95% CI: 1.23-1.65), respectively, compared to switching AD. However, these factors were not associated with the incidence of psychiatric conditions. Adding AAP increased hospitalization (OR = 1.25, 95% CI: 1.11-1.41), the number of inpatient days by 2.57-fold (95% CI: 1.75-3.76), and cost by 1.20-fold (95% CI: 1.02-1.40), compared to switching AD; adding AD did not show a significant association with these outcomes. CONCLUSIONS: In patients with MDD with inadequate responses to initial AD, TRD still occurred after subsequent treatments according to clinical guidelines. Since the effectiveness of second treatment strategies can differ in reality, further analysis of the clinical and economic evidence regarding second treatment strategies, such as adding AD or AAP, is needed using real-world data.

Cost-Effectiveness of Tiotropium in Elderly Patients with Severe Asthma Using Real-World Data.

BACKGROUND: Tiotropium has the potential to alleviate asthmatic symptoms caused by the aging of lungs. However, few studies have focused on specific treatments for elderly patients with asthma. OBJECTIVES: To estimate the cost-effectiveness of adding tiotropium to inhaled corticosteroids and long-acting beta-agonists in elderly patients with severe asthma using real-world data. METHODS: Phase I was a retrospective cohort study using the National Health Insurance claims data to measure clinical and economic outcomes. In phase II, a Markov model was constructed to evaluate cost-effectiveness from Korean health care system perspective, based on phase I, including 2 health states, and an asthma exacerbation event. We estimated cost given in 2018 US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Subgroup analyses for patients with poorly controlled symptoms (frequent short-acting beta-agonist users; frequent exacerbators) were performed. RESULTS: In elderly patients with severe asthma, the incremental cost and effectiveness in the tiotropium group compared with the inhaled corticosteroid and long-acting beta-agonist group were $2281 and 0.038 QALYs, respectively. The incremental cost-effectiveness ratio was $60,074/QALY, indicating that the addition of tiotropium is not a cost-effective alternative. Meanwhile, 2 subgroups with poorly controlled symptoms showed that adding tiotropium is a cost-effective alternative (frequent short-acting beta-agonist users $4078/QALY; frequent exacerbators $8332/QALY). CONCLUSIONS: Tiotropium shows a higher cost-effectiveness profile when applied to elderly patients with uncontrolled symptoms. These results using real-world evidence provide information beyond the clinical outcomes reported by randomized controlled trials, providing a complementary ground in establishing the reimbursement criteria of tiotropium for elderly patients with severe asthma.

Cost-effectiveness of antiviral treatment in adult patients with immune-tolerant phase chronic hepatitis B.

OBJECTIVE: The cost-effectiveness of antiviral treatment in adult immune-tolerant (IT) phase chronic hepatitis B (CHB) patients is uncertain. DESIGN: We designed a Markov model to compare expected costs and quality-adjusted life-years (QALYs) of starting antiviral treatment at IT-phase ('treat-IT') vs delaying the therapy until active hepatitis phase ('untreat-IT') in CHB patients over a 20-year horizon. A cohort of 10 000 non-cirrhotic 35-year-old patients in IT-phase CHB (hepatitis B e antigen-positive, mean serum hepatitis B virus (HBV) DNA levels 7.6 log10 IU/mL, and normal alanine aminotransferase levels) was simulated. Input parameters were obtained from previous studies at Asan Medical Center, Korea. The incremental cost-effectiveness ratio (ICER) between the treat-IT and untreat-IT strategies was calculated. RESULTS: From a healthcare system perspective, the treat-IT strategy with entecavir or tenofovir had an ICER of US$16 516/QALY, with an annual hepatocellular carcinoma (HCC) incidence of 0.73% in the untreat-IT group. With the annual HCC risk ≥0.54%, the treat-IT strategy was cost-effective at a willingness-to-pay threshold of US$20 000/QALY. From a societal perspective considering productivity loss by premature death, the treat-IT strategy was extremely cost-effective, and was dominant (ICER <0) if the HCC risk was ≥0.43%, suggesting that the treat-IT strategy incurs less costs than the untreat-IT strategy. The most influential parameters on cost-effectiveness of the treat-IT strategy were those related with HCC risk (HBV DNA levels, platelet counts and age) and drug cost. CONCLUSION: Starting antiviral therapy in IT phase is cost-effective compared with delaying the treatment until the active hepatitis phase in CHB patients, especially with increasing HCC risk, decreasing drug costs and consideration of productivity loss.