Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Cost-effectiveness of the 20-valent pneumococcal conjugate vaccine versus the 23-valent pneumococcal polysaccharide vaccine for older adults in South Korea.

BACKGROUND: Despite the demonstrated immunogenicity and safety of the 20-valent pneumococcal conjugate vaccine (PCV20) in older adults, the cost-effectiveness of the PCV20 was not examined compared to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in South Korea. Therefore, this study aimed to evaluate the cost-effectiveness of PCV20 compared with PPSV23 in adults aged 65 years and older in South Korea. METHODS: We constructed a Markov model that included susceptible states, invasive pneumococcal disease (IPD), non-bacteremic pneumonia (NBP), and death. The population was categorized by disease risk status (low risk, moderate risk, and high risk) and age group (65-74/75-84/85-99 years) at model entry. The annual incidence and mortality of IPD and NBP associated with PCV20 and PPSV23 were estimated based on serotype coverage, vaccine coverage, and vaccine effectiveness. The disease costs and utilities were obtained from previous studies. The incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness within the threshold of 16,824 USD per quality-adjusted life-year (QALY). RESULTS: Among the total population (n = 8,843,072), PCV20 prevented 1941 and 50,575 cases of IPDs and NBPs, respectively, and 898 and 8593 deaths due to IPDs and NBPs compared to PPSV23. The total medical cost per person was 12.11 USD higher in PCV20, with a gain of 0.0053 LYs and 0.0045 QALYs per person. The ICER for PCV20 and PPSV23 was 2270 USD/LY and 2677 USD/QALY. CONCLUSIONS: In South Korea, PCV20 is a cost-effective option compared with PPSV23 for adults aged 65 years and older. These cost-effectiveness results provide evidence for decision-making regarding the approval and National Immunization Program implementation of PCV20.

Systematic Review of the Economic Evaluation of Sodium-Glucose Cotransporter-2 Inhibitors Used as Treatment in Patients with Heart Failure.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been recently used as therapeutic agents for type 2 diabetes mellitus. Recent clinical trials have shown that they are beneficial for reducing the risk of cardiovascular mortality and hospitalization in patients with heart failure (HF). A comprehensive review regarding the cost-effectiveness of different SGLT2 inhibitors for HF treatment may be necessary to help clinicians and decision-makers select the most cost-effective HF treatment option. OBJECTIVE: This study conducted a systematic review of economic evaluation studies of SGLT2 inhibitors for the treatment of patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). METHOD: We searched PubMed, Cochrane, Embase, and EBSCOhost to identify published economic evaluation studies on SGLT2 inhibitors for HF treatment until May 2023. Studies on the economic evaluation of SGLT2 inhibitors in the treatment of HF were included. We extracted information such as country, population, intervention, type of model, health status, and conclusion of cost-effectiveness. RESULT: Of the 410 studies, 27 were finally selected. All economic evaluation studies used the Markov model, and commonly included health status as stable HF, hospitalization due to HF, and death. All dapagliflozin studies focused on patients with HFrEF (n = 13), and dapagliflozin was cost-effective in 14 countries, but not in the Philippines. All empagliflozin studies focused on the patients with HFrEF also showed the cost-effectiveness of empagliflozin (n = 11). However, empagliflozin use in patients with HFpEF was determined to be cost-effective in studies in Finland, China, and Australia studies but not in studies in Thailand and the USA. CONCLUSIONS: Most of the studies reported the cost-effectiveness of dapagliflozin and empagliflozin in patients with HFrEF. However, the cost-effectiveness of empagliflozin differed from country to country regarding patients with HFpEF. We suggest that further economic evaluation of SGLT2 inhibitors should focus on patients with HFpEF in more countries.

Hospital outcomes and costs for prostate cancer patients with comorbid heart failure by age group: An analysis of the US Nationwide Inpatient Sample.

RATIONALE, AIMS, AND OBJECTIVES: The prevalence of patients hospitalized with comorbid prostate cancer (PC) and heart failure (HF) has been steadily increasing. Both diseases share a set of common risk factors, with the most prominent being age. This study aimed to examine the outcomes and costs for patients with comorbid PC and HF, stratified by age. METHODS: We analyzed 41,340 hospitalization events of patients with PC using the US National Inpatient Sample from 2015 to 2018. Associations of HF with in-hospital mortality, length of stay (LOS), and hospital costs per hospitalization were measured using multivariable logistic regression, negative binomial regression, and generalized linear regression with log-link and gamma distribution, respectively, controlling for covariates. Subgroup analyses were performed for age groups <65 and ≥65. RESULTS: Visits of comorbid HF patients made up 2.3% (n = 952) of the PC study sample. Compared with PC patients without HF, those with HF had higher in-hospital mortality rates (odds ratio = 1.33, 95% confidence interval [CI] = 0.96-1.84, p = 0.085), longer hospital stays (incidence rate ratio = 1.32, 95% CI = 1.21-1.44, p < 0.001), and higher hospital costs (cost ratio = 1.17, 95% CI = 1.07-1.27, p = 0.001), controlling for covariates. On average, this amounted to a higher in-hospital mortality rate of 2.10%, an increased LOS of 1.73 days, and higher hospital costs of $2110 per patient. While in-hospital mortality did not differ significantly in patients aged <65 (p = 0.900), patients aged ≥65 had a 41% increased risk of in-hospital mortality compared with those without HF (p = 0.047). CONCLUSIONS: In comparison to those without HF, PC patients with comorbid HF showed higher rates of in-hospital mortality, LOS, and hospital costs, with mortality showing a significant difference exclusively in the ≥65 population. Effective management of older patients with PC is needed to improve outcomes and decrease costs.

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.

A systematic review of economic evaluations of tyrosine kinase inhibitors for non-small cell lung cancer (NSCLC).

INTRODUCTION: Although tyrosine kinase inhibitors (TKIs) have improved the efficacy of treatment for non-small cell lung cancer (NSCLC), the accessibility of TKIs is limited due to high costs. Despite the critical role of the cost-effectiveness of TKIs on decision-making, no systematic reviews have compared the cost-effectiveness of comparable TKIs. Therefore, we systemically reviewed the economic evaluation studies on various TKIs for NSCLC. AREAS COVERED: We searched PubMed and the Cochran Library to identify the published economic evaluation studies of TKIs in NSCLC patients that were published by January 2022. All of the included studies (n = 38) evaluated the cost-effectiveness of epidermal growth factor receptor (EGFR)-TKIs (n = 29) or anaplastic lymphocyte kinase (ALK)-TKIs (n = 9). The cost-effectiveness results were reported as the incremental cost-effectiveness ratio per quality-adjusted life-year, except for three studies. EXPERT OPINION: We found that the economic evaluation studies of the first and second generation of EGFR-TKIs and ALK-TKIs varied by the country and study settings, such as comparator and input parameters. In 12 studies, osimertinib (EGFR-TKI) was not cost-effective compared to other first/second EGFR-TKIs, regardless of the study settings. More evidence can be provided about cost-effectiveness of the third-generation TKIs in future research.

Health-related quality of life among elderly breast cancer patients treated with adjuvant endocrine therapy: a U.S Medicare population-based study.

OBJECTIVES: The evidence regarding the impact of individual adjuvant endocrine therapies (AET) on health-related quality of life (HRQoL) is limited. We aimed to assess the association between the type of AET and HRQoL and to examine the relationship between HRQoL and one-year mortality among women with breast cancer in the USA. METHODS: This retrospective cross-sectional study used the 2006-2017 Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey database to identify older women with early-stage hormone receptor-positive breast cancer. Multivariate linear regressions were used to assess the association between types of AET (anastrozole, letrozole, exemestane, and tamoxifen) and HRQoL scores (physical component summary (PCS) and mental component summary (MCS)). Multivariate logistic regressions were used to predict the impact of PCS and MCS on one-year mortality. RESULTS: Out of 3537 older women with breast cancer, anastrozole was the most commonly prescribed (n = 1945, 55.0%). Regarding PCS, there was no significant difference between the four AET agents. Higher MCS scores, which indicate better HRQoL, were reported in patients treated with anastrozole (vs. letrozole [ß = 1.26, p = 0.007] and exemestane [ß = 2.62, p = 0.005) and tamoxifen (vs. letrozole [ß = 1.49, p = 0.010] and exemestane [ß = 2.85, p = 0.004]). Lower PCS and MCS scores were associated with higher one-year mortality, regardless of type of AET initiated, except for tamoxifen in MCS. CONCLUSION: Although there was no significant difference in physical HRQoL scores between AET agents, anastrozole and tamoxifen were associated with better mental HRQoL scores.

In-hospital mortality, length of stay and hospital costs for hospitalized breast cancer patients with comorbid heart failure in the USA.

OBJECTIVES: Breast cancer and heart failure (HF) are frequently interconnected due to shared risk factors and the cardiotoxicity of breast cancer treatment. However, the association between HF and hospital outcomes among breast cancer patients has not been studied. This study examined the association between HF and hospital outcomes among hospitalized patients with breast cancer. METHODS: This cross-sectional study using the 2015-2018 Healthcare Cost and Utilization Project-National Inpatient Sample data included hospitalized women who were aged 18 years or older and had a primary diagnosis code for breast cancer. Logistic regression, negative binomial regression, and generalized linear models with log-link and gamma distribution were used to assess the associations of HF with in-hospital mortality, length of stay (LOS) and hospital costs. RESULTS: Among 17,335 hospitalized patients with breast cancer, 4.2% (n = 1021) had HF. Compared to breast cancer patients without HF, those with HF were more likely to die during hospitalization (odds ratio = 1.65, 95% CI = 1.27-2.16, p < .001), stay in the hospital longer (incidence rate ratio = 1.22, 95% CI = 1.15-1.30, p < .001) and have higher hospital costs (cost ratio = 1.09, 95% CI = 1.03-1.14, p = .003) during hospitalization, controlling for covariates. CONCLUSION: HF has a substantial negative impact on health outcomes among hospitalized breast cancer patients. Breast cancer and HF are often considered separate medical conditions, but promoting effective management of comorbid HF in breast cancer patients may help to improve hospital outcomes in this population.

Hospital outcomes of male breast cancer in the United States.

OBJECTIVES: Hospital utilization and costs of female breast cancer have been well documented. However, evidence focusing on male breast cancer is scarce, despite the different clinical characteristics between female and male breast cancer. We aim to estimate hospital length of stay (LOS) and costs associated with male breast cancer in the United States. STUDY DESIGN: Retrospective observational study. METHODS: We analyzed the 2012-2016 Health Care Utilization Project National Inpatient Sample of 416 hospitalization events of male patients with breast cancer. Patients who had breast cancer diagnoses were selected based on the primary International Classification of Disease, Ninth Revision or Tenth Revision, Clinical Modification codes. A negative binomial regression and a generalized linear model with a gamma distribution and log-link function were conducted to estimate the LOS and hospital costs after controlling for sociodemographics, clinical characteristics (eg, metastatic status, Elixhauser Comorbidity Index [ECI] score), and hospital characteristics. RESULTS: On average, male patients with breast cancer stayed for 2.42 days and expensed $9059 per hospital visit. Patients with metastatic status had longer LOS (5.39 vs 3.24 days; P = .005) and higher hospital costs ($11,185 vs $8547; P = .03) than those without. Patients with an ECI score of 3 or more showed longer LOS (4.05 vs 2.68 days; P = .003) and higher hospital costs ($10,043 vs $7022; P < .001) than those with an ECI score of 0. CONCLUSIONS: LOS and hospital costs for male patients with breast cancer were associated with metastatic status and comorbidities. This information can be used to assess the health care resources needed to treat male breast cancer.

Association of congestive heart failure with hospital outcomes among renal cancer patients in the United States: analysis of nationwide inpatient sample.

Background: Patients with renal cancer are at increased risk of comorbid congestive heart failure (CHF) due to several shared risk factors and the cardiotoxicity of some medications used for renal cancer treatment. We aimed to examine the relationship between CHF and hospital outcomes among renal cancer patients in the U.S.Methods: In this cross-sectional study, we identified hospitalizations of renal cancer patients using the 2015-2017 National Inpatient Sample. We assessed the relationship between CHF and hospital outcomes in this patient population, including in-hospital mortality, length-of-stay (LoS), and hospital costs.Results: Among the 20,321 hospitalizations of renal cancer patients identified, 6.1% involved patients with comorbid CHF (n = 1,231). The odds of in-hospital mortality did not differ based on CHF presence (odds ratio = 1.21; p = 0.354). Hospitalizations of renal cancer patients with CHF were associated with a greater LoS (incidence rate ratio = 1.44; p < 0.001) and higher hospital costs (cost ratio = 1.27; p < 0.001) than those without CHF.Conclusions: CHF in renal cancer patients is associated with increased LoS and higher hospital costs. These findings suggest that optimal management of comorbid CHF may improve hospital outcomes in patients with renal cancer and provides evidence to support the emerging field of cardio-oncology.

Cost-effectiveness analyses of targeted therapy and immunotherapy for advanced non-small cell lung cancer in the United States: a systematic review.

Introduction: Mutation-targeting and immuno-oncology drugs are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). Cost-effectiveness analyses (CEA) of these drugs have been conducted using various analytical methods and cost-effectiveness thresholds. This systematic review provides a comprehensive summary of the available evidence.Area covered: PubMed, Embase, and Cochrane Library were used to select for CEA of targeted therapies for NSCLC in the United States published between 2008 and 2020. Among the 28 included studies, a majority were published from 2017 to 2020 (n = 18) and more than half targeted non-squamous NSCLC (n = 15). The most frequently evaluated therapy was pembrolizumab (n = 11), followed by bevacizumab (n = 8) and erlotinib (n = 4). After 2009, all included studies applied $100,000 or more thresholds. Thresholds of studies supported by industry (median = $150,000) were more distributed than those of studies supported by nonprofits (median = $100,000).Expert commentary: Medications of interest have changed and are individualized to particular mutations. The cost-effectiveness thresholds varied among sponsors but generally trended to increase over time. This review provides an overview of the available cost-effectiveness findings for stakeholders and contributes to evidence-based practice.

The economic impact of disease progression and death in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer patients: using Korean nationwide health insurance claims data.

OBJECTIVES: Recognizing the value of anticancer treatments based on progression-free survival and overall survival may help decision making in healthcare policy. We aimed to measure and compare the impact of disease progression and terminal state prior to death on healthcare costs in HR+, HER2- ABC patients. METHODS: We conducted a retrospective study using Korean nationwide health insurance claims database between 1 September 2012 and 31 August 2017. The impact of disease progression was estimated by measuring the average incremental monthly cost per patient during 1 year after progression compared to 1 year before progression. Death-related costs per patient per month (PPPM) were measured for those who died within 1 year after progression. Generalized estimating equation (GEE) was used to estimate the variations in PPPM costs by progression and death with adjustment for clinical factors. RESULTS: After progression, 1,636 patients expensed $2,892 per month more on average than before progression ($3762 vs. $870). The GEE analysis with adjustment for baseline characteristics showed that PPPM costs increased by 3.46 folds (95% CI = 3.06-3.93) after progression. Also, PPPM costs were 1.74 (95%CI = 1.43-2.12) times higher in patients who died within 1 year after progression relative to survived patients. When considering the interaction between progression and death, deceased patients showed higher increased ratio of PPPM costs after progression (4.91; p=value<.0001) than survived patients (2.95; 95% CI = 2.61-3.34). CONCLUSIONS: From the payer's perspective, more healthcare costs incurred during the progression state than terminal state in HR+, HER2- ABC patients. The impact of disease progression emphasizes the importance of effectively treating HR+, HER2- ABC patients.

Economic evaluations of oral medications for breast cancer treatment in the U.S.: a systematic review with a focus on cost-effectiveness threshold.

Introduction: With the advent of targeted therapy, the U.S. Food and Drug Administration has recently approved several oral anticancer medications (OAMs) for breast cancer (BC). Despite the improved effectiveness of those OAMs, the high financial burden is an issue. Evidence from cost-effectiveness analysis (CEA) can provide valuable information for decision-makers when deciding whether to use these high-priced medications. Many CEAs on OAMs have been conducted using various analytical approaches and cost-effectiveness thresholds (CETs). However, there is no comprehensive systematic review of CEAs across all OAMs.Area covered: PubMed and Cochrane library were used to select for CEAs of OAM for BC in the U.S. published by May 2019. Among the 25 included studies, studies published between 1993 and 2011 analyzed either early BC (n = 11) or advanced/metastatic BC (n = 5), those between 2012-2019 analyzed advanced/metastatic BC (n = 9). Studies including targeted therapies were published after 2009. The CETs tended to increase over time and were higher in the studies for advanced/metastatic BC (median = $125,000) than those for early BC (median = $50,000).Expert commentary: The target population and medications of interest have changed and the methods of articles have evolved. The range of CETs tends to differ by study setting with an increase over time.

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.

The Utility of 5 Hypothetical Health States in Heart Failure Using Time Trade-Off (TTO) and EQ-5D-5L in Korea.

BACKGROUND AND OBJECTIVE: Utility provides a preference for specific health state in economic evaluation, and they obtained from general population could be useful in respect of societal resource allocation. We aimed to investigate the utilities of health states for heart failure (HF), a major and growing public health problem, related to hospitalization and adverse drug effects by interrogating the general Korean population. METHODS: Five health states for patients with HF were developed based on literature reviews: stable chronic heart failure (SCHF), hospitalization, SCHF + cough, SCHF + hypotension, and SCHF + hyperkalemia. We selected 100 individuals from the general population through quota sampling by age, sex, and region, and conducted face-to-face interviews. We measured utilities for 5 hypothetical health states of HF using both time trade-off (TTO) and EuroQol-5 dimensions-5 levels (EQ-5D-5L). Repeated-measures analysis of variance compared the utilities between all health states for each instrument. To identify the factors affecting the utility, a linear mixed model (LMM) analysis was performed. RESULTS: The mean utility value for SCHF, SCHF + cough, SCHF + hypotension, SCHF + hyperkalemia, and hospitalization was calculated as 0.815, 0.732, 0.646, 0.548, and 0.360, respectively, by using TTO. The respective values using EQ-5D-5L were 0.871, 0.793, 0.710, 0.589, and 0.215. The utilities for HF significantly differed between all health states in each instrument (p < 0.001). In LMM analysis, hospitalization had a significantly negative effect on the utilities of both instruments. CONCLUSIONS: The utilities decreased in order of SCHF, SCHF + cough, SCHF + hypotension, SCHF + hyperkalemia, and hospitalization. These results can be useful for decision making in resource allocation for HF interventions.

Eliciting societal preferences of reimbursement decision criteria for anti cancer drugs in South Korea.

INTRODUCTION: In order to look beyond the cost-effectiveness analysis, this study used a multi-criteria decision analysis (MCDA), which reflects societal values with regard to reimbursement decisions. This study aims to elicit societal preferences of the reimbursement decision criteria for anti cancer drugs from public and healthcare professionals. METHODS: Eight criteria were defined based on a literature review and focus group sessions: disease severity, disease population size, pediatrics targets, unmet needs, innovation, clinical benefits, cost-effectiveness, and budget impacts. Using quota sampling and purposive sampling, 300 participants from the Korean public and 30 healthcare professionals were selected for the survey. Preferences were elicited using an analytic hierarchy process. RESULTS: Both groups rated clinical benefits the highest, followed by cost-effectiveness and disease severity, but differed with regard to disease population size and unmet needs. Innovation was the least preferred criteria. CONCLUSIONS: Clinical benefits and other social values should be reflected appropriately with cost-effectiveness in healthcare coverage. MCDA can be used to assess decision priorities for complicated health policy decisions, including reimbursement decisions. It is a promising method for making logical and transparent drug reimbursement decisions that consider a broad range of factors, which are perceived as important by relevant stakeholders.

Cost-effectiveness Analysis of Treatment Sequence Initiating With Etanercept Compared With Leflunomide in Rheumatoid Arthritis: Impact of Reduced Etanercept Cost With Patent Expiration in South Korea.

PURPOSE: In south Korea, the price of biologics has been decreasing owing to patent expiration and the availability of biosimilars. This study evaluated the cost-effectiveness of a treatment strategy initiated with etanercept (ETN) compared with leflunomide (LFN) after a 30% reduction in the medication cost of ETN in patients with active rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX-IR). METHODS: A cohort-based Markov model was designed to evaluate the lifetime cost-effectiveness of treatment sequence initiated with ETN (A) compared with 2 sequences initiated with LFN: LFN-ETN sequence (B) and LFN sequence (C). Patients transited through the treatment sequences, which consisted of sequential biologics and palliative therapy, based on American College of Rheumatology (ACR) responses and the probability of discontinuation. A systematic literature review and a network meta-analysis were conducted to estimate ACR responses to ETN and LFN. Utility was estimated by mapping an equation for converting the Health Assessment Questionnaire-Disability Index score to utility weight. The costs comprised medications, outpatient visits, administration, dispensing, monitoring, palliative therapy, and treatment for adverse events. A subanalysis was conducted to identify the influence of the ETN price reduction compared with the unreduced price, and sensitivity analyses explored the uncertainty of model parameters and assumptions. FINDINGS: The ETN sequence (A) was associated with higher costs and a gain in quality-adjusted life years (QALYs) compared with both sequences initiated with LFN (B, C) throughout the lifetime of patients with RA and MTX-IR. The incremental cost-effectiveness ratio (ICER) for strategy A versus B was ₩13,965,825 (US$1726) per QALY and that for strategy A versus C was ₩9,587,983 (US$8050) per QALY. The results indicated that strategy A was cost-effective based on the commonly cited ICER threshold of ₩20,000,000 (US$16,793) per QALY in South Korea. The robustness of the base-case analysis was confirmed using sensitivity analyses. When the unreduced medication cost of ETN was applied in a subanalysis, the ICER for strategy A versus B was ₩20,909,572 (US$17,556) per QALY and that for strategy A versus C was ₩22,334,713 (US$18,753) per QALY. IMPLICATIONS: This study indicated that a treatment strategy initiated with ETN was more cost-effective in patients with active RA and MTX-IR than 2 sequences initiated with LFN. The results also indicate that the reduced price of ETN affected the cost-effectiveness associated with its earlier use.

Cost-effectiveness of Tofacitinib in the Treatment of Moderate to Severe Rheumatoid Arthritis in South Korea.

PURPOSE: This study evaluated the cost-effectiveness of introducing tofacitinib, an oral Janus kinase inhibitor, to the treatment of Korean patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs. METHODS: In this cost-utility analysis model, patients transitioned through treatment sequences based on Korean guidelines for RA patients with inadequate response to conventional disease-modifying antirheumatic drugs. Lifetime health-related quality of life and costs were evaluated. Characteristics of the model cohort were based on those reported by the Oral Rheumatoid Arthritis phase 3 triaL (ORAL) Standard randomized Controlled trial of tofacitinib or adalimumab versus placebo. Efficacy was assessed using American College of Rheumatology response rates, converted to the changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, based on tofacitinib clinical trials data. Published clinical trial data on discontinuation rates of the indicated drugs were incorporated in the model. The HAQ-DI scores were mapped onto utility values to calculate outcomes in terms of quality-adjusted life-years (QALYs); HAQ-DI-to-utility (EuroQoL 5D) mapping was based on data from 5 tofacitinib clinical trials. Costs were analyzed from a societal perspective, with values expressed in 2013 Korean won (KRW). Cost-effectiveness is presented in terms of incremental cost-effectiveness ratios (ICERs). One-way sensitivity analyses were performed to assess the robustness of the model. FINDINGS: First-line tofacitinib used before the standard of care (base-case analysis) increased both treatment costs and QALYs gained versus the standard-of-care treatment sequence, resulting in an ICER of KRW 13,228,910 per QALY. Tofacitinib also increased costs and QALYs gained when incorporated as a second-, third-, or fourth-line therapy. The inclusion of first-line tofacitinib increased the duration of active immunomodulatory therapy from 9.4 to 13.2 years. Tofacitinib-associated increases in costs were attributable to the increased lifetime drug costs. In sensitivity analyses, variations in input parameters and assumptions yielded ICERs in the range of KRW 6,995,719 per QALY to KRW 37,450,109 per QALY. IMPLICATIONS: From a societal perspective, the inclusion of tofacitinib as a treatment strategy for moderate to severe RA is cost-effective; this conclusion was considered robust based on multiple sensitivity analyses. The study was limited by the lack of clinical data on follow-up therapy after tofacitinib administration and a lack of long-term data on discontinuation of drug use.