Cost-Effectiveness of Clopidogrel vs Aspirin Monotherapy After Percutaneous Coronary Intervention: Results From the HOST-EXAM Study.

Background: The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Disease-Extended Antiplatelet Monotherapy) trial showed superior efficacy and safety of clopidogrel monotherapy compared with aspirin monotherapy during the chronic maintenance period after percutaneous coronary intervention (PCI). Objectives: The goal of this study was to investigate the cost-effectiveness of clopidogrel monotherapy compared with that of aspirin monotherapy. Methods: A Markov model was developed for patients in the stable phase after PCI. From the perspectives of the South Korean, UK, and U.S. health care systems, the lifetime health care costs and quality-adjusted life-years (QALYs) of each strategy were estimated. Transition probabilities were obtained from the HOST-EXAM trial, and health care costs and health-related utilities were obtained from data and literature for each country. Results: From the perspective of the South Korean health care system, the base-case analysis showed that clopidogrel monotherapy was $3,192 higher in lifetime health care costs and 0.139 lower in QALYs compared with aspirin. This result was greatly influenced by the numerically but insignificantly higher cardiovascular mortality of clopidogrel compared with aspirin. In the analogous UK and U.S. models, clopidogrel monotherapy was projected to decrease health care costs by £1,122 and $8,920 per patient compared with aspirin monotherapy while reducing QALYs by 0.103 and 0.175, respectively. Conclusions: Based on empirical data from the HOST-EXAM trial, clopidogrel monotherapy was projected to lead to reduced QALYs compared with aspirin during the chronic maintenance period after PCI. These results were affected by a numerically higher rate of cardiovascular mortality in clopidogrel monotherapy reported from the HOST-EXAM trial. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).

Markov Chain Models for Cardiac Rhythm Dynamics in Patients Undergoing Catheter Ablation of Atrial Fibrillation.

We have developed a novel Markov Chain modeling system that considers vectors of patients with atrial fibrillation (AF) by their AF status over a period of time. Our model examines the impact of catheter ablation of AF upon the dynamics of a patient's AF status and their potential return to sinus rhythm. We prove several theorems to determine the probabilities of patients achieving sinus rhythm or progressing to permanent AF. Additionally, we observed aggregation of patients within the paroxysmal AF state in simulation. The aggregating property of Markov chains illustrated the potential benefits of catheter ablation on healthcare resource allocation.

A Tale of Two Social Insurance Systems in South Korea and Taiwan: A Financial Risk Protection Perspective.

Universal Health Coverage (UHC) is a widespread policy goal in the 21st century. The aim is to protect people from financial risk while promoting their access to good-quality care. This study examined the social insurance systems of South Korea and Taiwan to explore the critical challenges of achieving effective UHC. By assessing the impact of UHC on financial risk protection (measured by out-of-pocket payment share and catastrophic payment headcount), we found that when South Korea inaugurated its National Health Insurance (NHI) program with a limited benefits package and high cost sharing, it did not reduce the financial burden. Meanwhile, we observed a drop of 5 to 6 percentage points in the catastrophic payment headcount in Taiwan, which offered a universal and rather comprehensive benefits package with a modest cost-sharing design under its single-payer NHI system. The political-economic context of the UHC policy evolution was further explored through an in-depth discussion. We conclude that to provide sufficient financial risk protection against unexpected medical expenses, the design of the insurance scheme, in particular the risk-sharing mechanism, not only matters but is also the key to success.

Korean Guidelines for Pharmacoeconomic Evaluations: Updates in the Third Version.

The first version of the pharmacoeconomic (PE) guidelines was published in South Korea in 2006. Despite its first revision in 2011, there were still ambiguities in its interpretation. Moreover, methodologies for estimating effectiveness and costs have also evolved since then. Under these circumstances, the Health Insurance Review and Assessment Service published the third version in January 2021. This article reviews the revision process and major changes made in the new edition of the PE guidelines. The revision was processed through reviews of the previous 50 PE submissions, international guidelines, academic literature, and surveys and advisory meetings to obtain stakeholders' opinions. The analysis perspective has changed from a limited societal perspective to a healthcare system perspective. In addition to the drug with the highest market share, drugs used in clinical trials can be selected as comparators under certain conditions. The discount rate decreased from 5% to 4.5%. Furthermore, the revised guidelines provide more detailed and specific instructions for items including non-inferiority margin, extrapolation, utility elicitation, and uncertainty. Treatment switch and co-dependent technology guidelines are newly included; the budget impact analysis guideline is deleted. Through this revision, transparency and consistency of decision-making is expected to improve.

Equity of health care financing in South Korea: 1990-2016.

BACKGROUND: The National Health Insurance in Korea has been in operation for more than 30 years since having achieved universal health coverage in 1989 and has gone through several policy reforms. Despite its achievements, the Korean health insurance has some shortfalls, one of which concerns the fairness of paying for health care. METHOD: Using the population representative Household Income and Expenditure Survey data in Korea, this study examined the yearly changes in the vertical equity of paying for health care between 1990 and 2016 by the source of financing using the Kakwani index, considering health insurance and other related policy reforms in Korea during this period. RESULTS: The study results suggest that direct tax was the most progressive mode of health care financing in all years, whereas indirect tax was proportional. The out-of-pocket payments were weakly regressive in all years. The Kakwani index for health insurance contributions was regressive but now is proportional to the ability to pay, whereas the Kakwani index for private health insurance premiums turned from progressive to weakly regressive. The Kakwani index for overall health care financing showed a weak regressivity during the study period. DISCUSSION: The overall health care financing in Korea has transformed from a slight regressivity to proportional over time between 1990 and 2016. It is expected that these changes were closely related to the improved equity of health insurance contributions from 1998 to 2008, which was the result of a merger of the health insurance societies and an amendment in the health insurance contribution structure. These results suggest that standardizing insurance managing organizations and financing rules potentially has positive implications for the equity of healthcare financing in a country where the major method of health care financing is social health insurance.

Patent challenges and factors associated with successful patent challengers under the patent linkage system: recent evidence from South Korea after the Korea United States free trade agreement.

OBJECTIVES: The patent linkage system upgraded patent challenges to an important factor in granting timely market approval for generic drugs. We aim to understand patent challenges and identify the factors that are associated with successful patent challengers under the patent linkage system in South Korea. METHODS: We constructed a novel dataset that combined information on manufacturers with detailed data about their patent challenges after introduction of the patent linkage system. Based on the number of successful patent challenges, manufacturers were categorized into non-challengers, passive challengers, and aggressive challengers. Then, two types of logistic models were applied to identify the factors associated with successful and aggressive challengers. FINDINGS: Only 39 active ingredients were challenged by 77 manufacturers from March 2015 to December 2019. Of 171 manufacturers, 94 (55 %) were non-challengers, 58 (34 %) were passive challengers who had succeeded in fewer than 4 patent challenges, and 19 (11 %) were aggressive challengers who had succeeded in 4 or more patent challenges. Higher sales, more employees, and a greater number of reimbursed drugs were associated with being a patent challenger, while a greater number of reimbursed drugs was associated with being an aggressive challenger. CONCLUSION: Some manufacturers utilize patent challenges to strengthen their product portfolios in the market. However, under the patent linkage system, the frequency of patent challenges is limited in South Korea compared to the United States. In particular, patent challenges against drugs in injection form and biologics are very rare.

Cost-effectiveness of using amyloid positron emission tomography in individuals with mild cognitive impairment.

BACKGROUND: Amyloid positron emission tomography (PET) makes it possible to diagnose Alzheimer's disease (AD) in its prodromal phase including mild cognitive impairment (MCI). This study evaluated the cost-effectiveness of including amyloid-PET for assessing individuals with MCI. METHODS: The target population was 60-year-old patients who were diagnosed with MCI. We constructed a Markov model for the natural history of AD with the amyloid positivity (AP). Because amyloid-PET can detect the AP MCI state, AD detection can be made faster by reducing the follow-up interval for a high-risk group. The health outcomes were evaluated in quality-adjusted life years (QALYs) and the final results of cost-effectiveness analysis were presented in the form of the Incremental Cost-Effectiveness Ratio (ICER). To handle parameter uncertainties, one-way sensitivity analyses for various variables were performed. RESULTS: Our model showed that amyloid-PET increased QALYs by 0.003 in individuals with MCI. The estimated additional costs for adopting amyloid-PET amounted to a total of 1250 USD per patient when compared with the cost when amyloid-PET is not adopted. The ICER was 3,71,545 USD per QALY. According to the sensitivity analyses, treatment effect of Donepezil and virtual intervention effect in MCI state were the most influential factors. CONCLUSIONS: In our model, using amyloid-PET at the MCI stage was not cost-effective. Future advances in management of cognitive impairment would enhance QALYs, and consequently improve cost-effectiveness.

The Association Between the Basic Old-Age Pension and Depression of the Older Adults in Korea.

OBJECTIVES: The purpose of this study was to investigate the association between the Basic Old-Age Pension (BOP), which is a noncontributory pension, and depression in BOP beneficiaries in Korea. METHODS: We used the second and third waves (2007-2008) of the Korea Welfare Panel Study to identify the effect of the BOP on mental health in the year of its introduction. The Center for Epidemiological Studies-Depression Scale, applied in a Korean context, was used to evaluate mental health. To analyze the effect of the BOP, a difference-in-difference approach was used in analyses of all subjects and subgroups. RESULTS: For this study population of 760 adults, the BOP did not have a statistically significant relationship with depression in its beneficiaries. After controlling for type of household, the BOP was still not associated with lower reporting of depression, either in single-beneficiary or double-beneficiary households, in the year of the benefit. CONCLUSIONS: The BOP policy had no significant relationship with the level of depression among recipients. However, this should not be interpreted as implying that income subsidy programs for older adults, such as the BOP, do not affect mental health, considering the importance of economic hardship in this population and the program's socioeconomic effects.

Marketing and Pricing Strategies of Blockbuster Drugs in the South Korean Market: A 15-Year Retrospective Cohort Study for Choline Alfoscerate.

INTRODUCTION: Understanding marketing strategies and price competition among manufacturers is essential to manage health care expenditures, particularly those related to blockbuster drugs. OBJECTIVES: To assess marketing and pricing strategies of blockbuster drugs in South Korea. METHODS: Baseline information on manufacturers who were granted marketing approval for choline alfoscerate in various forms was retrieved. Accumulation of manufacturers in the market was also identified, and manufacturers were categorized into first movers and latecomers based on their marketing time. Then, an event history analysis and a regression analysis were applied to estimate the duration of marketing and their price competition. RESULTS: Currently, 109, 83, and 26 manufacturers produce choline alfoscerate in capsule, tablet, or syrup form, respectively, indicating that many manufacturers have marketed generics and the majority of the generics are categorized as latecomers. The size of the manufacturer was a significant factor in marketing new medicines, while the variable was not related to the marketing of modified drugs. Furthermore, price competition in the market was rare and only a few major firms initiated price competition. CONCLUSION: The Korean market appears to be an example of perfect competition when we focus on the number of manufacturers. However, the market is near-monopolistic when examining the price of generic drugs. While product competition between different forms of drugs is effective in lowering price, product competition within the same form of a drug does not exist in the market.

Understanding of for whom, under what conditions and how the compulsory licensing of pharmaceuticals works in Brazil and Thailand: A realist synthesis.

When pharmaceuticals are not fully available mainly due to the high cost of medicines, a government can issue compulsory licensing (CL). It is well documented that Brazil and Thailand have notably attempted CL. A realist review was undertaken to understand the identical social interventions in comparative settings, and to draw practical implications for attempting CL relevant for middle-income countries in the era of high-cost medicines. CL is not only a politically well-devised measure to achieve universal health coverage, but also a tentative commitment, which is determined both at the country level and at the global level. At the country level, political will, with catalytic roles of civil activism, is important in order to guarantee the right to health. Through this will, the governments can achieve universal health coverage. In addition, electoral systems, political leaders, and a constitution are necessary to attempt CL. In addition, CL should operate along with other policy instruments, including a comprehensive essential medicines list, CL-friendly phrasing in patent law, and a competent pharmaceutical industry. At the global level, the balance of power between the WTO regime and the global justice movement is critical. This provides global-level context that can either encourage or prevent CL.

Moderating the impact of patent linkage on access to medicines: lessons from variations in South Korea, Australia, Canada, and the United States.

BACKGROUND: The inclusion of patent linkage mechanisms in bilateral and plurilateral trade and investment agreements has emerged as a key element in the United States' TRIPS-Plus intellectual property (IP) negotiating agenda. However, the provisions establishing patent linkage mechanisms in several agreements appear to reflect a degree of ambiguity, potentially enabling some flexibility in their implementation. In this study, we reviewed the features of the prototypic patent linkage mechanism established by the Hatch-Waxman Act in the United States, and compared these with the implementation of systems in three countries whose agreements with the US include patent linkage obligations. From these analyses, we draw lessons for moderating the impact of these mechanisms on access to generic medicines. METHODS: We reviewed the features of the patent linkage mechanism in the US, and undertook a detailed analysis of relevant treaty provisions and the manner of implementation in Canada, Australia, and South Korea. RESULTS: A key difference between the US implementation of patent linkage and that of its trading partners is the disparate treatment afforded to biologics. Because of the significant differences in the regulatory frameworks applying to small molecule and biologic medicines in the US, the Hatch- Waxman provisions do not apply to biologics and they are not subject to patent linkage. By contrast, the regulatory frameworks in Canada, Australia and South Korea do not reflect similar distinctions and thus patent linkage mechanisms also capture biologics. Additional variations in implementation, mainly the result of constructive ambiguities in the respective treaty texts, offer potential opportunity for mitigating the adverse impact of patent linkage provisions on market entry of generic medicines. Practical measures include ensuring the availability of an accessible, transparent and easily searchable database of patent information; avoiding automatic stays of generic marketing approval where possible; and requiring certification by rights holders to prevent abuse of the system. CONCLUSIONS: Where countries accept treaty obligations to establish patent linkage mechanisms, the impact on access to generic medicines may be moderated to a degree by retaining and exploiting constructive ambiguities in the treaty text and addressing practical aspects of implementation.

Compulsory licensing of pharmaceuticals reconsidered: Current situation and implications for access to medicines.

To examine patterns and trends in attempts, distinguished from issuance, to issue compulsory licensing of pharmaceuticals and to assess related implications in the era of high-cost medicines. Documents from various civil society organisations were primarily used to search attempts, as well as published literature. The identified attempts were analysed by pharmaceutical level, national level, claimers, and the outcomes of the attempts. There have been 108 attempts to issue compulsory licensing for 40 pharmaceuticals in 27 countries since 1995. Most of the attempts were in Asian, Latin American, and African countries and mainly for HIV/AIDS medicines. Moreover, when the claimer was the government, the likelihood of approval and positive outcomes increased. Compulsory licensing, which was devised to cope with the HIV/AIDS pandemic in low-income countries, became a practical measure in several Asian and Latin American countries, even for non-HIV/AIDS medicines. Resurgent compulsory licensing in 2012 and 2014, influenced by the global justice movement, might represent a policy window in the near future as the Doha Declaration did in the 2000s. In this context, various experiences should be circulated and analysed at the global level to better understand the circumstances under which successful issuance has been achieved at the country level.

The trends and constructive ambiguity in international agreements on intellectual property and pharmaceutical affairs: Implications for domestic legislations in low- and middle-income countries.

The purpose of this study is to analyse the trends in international agreements including Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), Korea-United States Free Trade Agreements, and Trans-Pacific Partnership Agreements on intellectual property and pharmaceutical affairs with the updated framework. The study also assesses constructive ambiguity in international agreements, which might affect the implementation process through interpretation and domestic legislations. Five flexibility clauses and three TRIPS-plus provisions were selected, and presence of constructive ambiguity in the agreements was analysed to draw actual trends in international agreements. Flexibility provisions excluding compulsory licensing were not noticeably changed, and TRIPS-plus provisions including data exclusivity and patent linkage were expanded in scope or newly appeared, respectively. The clause regarding compulsory licensing, extension of the patent term, data exclusivity, and patent linkage showed unclear definitions or the lack of adequate explanations. With constructive ambiguity in those clauses, a country who wants to join international agreements in the near future could amend domestic legislations to minimise the detrimental effect of international agreements on access to medicines.

Has the Copayment Ceiling Improved Financial Protection in the Korean National Health Insurance System? Evidence From the 2009 Policy Change.

OBJECTIVES: To relieve the financial burden faced by households, the Korean National Health Insurance (NHI) system introduced a "copayment ceiling," which evolved into a differential ceiling in 2009, with the copayment ceiling depending on patients' income. This study aimed to examine the effect of the differential copayment ceiling on financial protection and healthcare utilization, particularly focusing on whether its effects varied across different income groups. METHODS: This study obtained data from the Korea Health Panel. The number of households included in the analysis was 6555 in 2008, 5859 in 2009, 5539 in 2010, and 5372 in 2011. To assess the effects of the differential copayment ceiling on utilization, out-of-pocket (OOP) payments, and catastrophic payments, various random-effects models were applied. Utilization was measured as treatment days, while catastrophic payments were defined as OOP payments exceeding 10% of household income. Among the right-hand side variables were the interaction terms of the new policy with income levels, as well as a set of household characteristics. RESULTS: The differential copayment ceiling contributed to increased utilization regardless of income levels both in all patients and in cancer patients. However, the new policy did not seem to reduce significantly the incidence of catastrophic payments among cancer patients, and even increased the incidence among all patients. CONCLUSIONS: The limited effect of the differential ceiling can be attributed to a high proportion of direct payments for services not covered by the NHI, as well as the relatively small number of households benefiting from the differential ceilings; these considerations warrant a better policy design.

Inequalities in health care utilization for common childhood illnesses in Ethiopia: evidence from the 2011 Ethiopian Demographic and Health Survey.

BACKGROUND: Globally, 5.9 million children under the age of five died in 2015. More than half and almost one-third of those deaths occurred in sub-Saharan Africa and South Asia, respectively. Diarrhea and Pneumonia, which were the major causes of the problem, accounted for more than two million deaths of the world's youngest children every year. Like other developing countries, child health services utilization is low in Ethiopia. The aim of this study was to identify the determinant factors for the inequalities in medical treatment seeking behavior for common childhood illnesses in Ethiopia. METHODS: Data were obtained from the Ethiopian Demographic and Health Survey (EDHS) 2011. All children who had diarrhea, cough, and fever in the 2 weeks preceding the survey were included. A total of 1620 children with diarrhea, 2082 with fever, and 2134 with cough were included in the analyses. Multivariate logistic regression with a 95% confidence interval, adjusted odds-ratio, and a P < 0.05 were used to determine the independent effect of each variable. RESULTS: Household wealth-status, maternal and paternal education, and religion were found to be associated with the inequality in the use of child health services. Respondents from households with the richest, richer, and middle wealth status had higher odds of seeking medical treatment for childhood diarrhea, cough, and fever than that of the poorest ones. Maternal and paternal educational status was also associated with medical treatment seeking behavior for childhood diarrhea and fever, respectively. CONCLUSION: Household wealth and educational status of parents were possible determinant factors for the inequalities observed in health care seeking behavior. Policy interventions aimed at improving the appropriate medical treatment seeking behavior for common childhood illnesses are desirable. Practical economic policies aimed at moving those in the lower wealth quintile are essential to bridge the gap between the rich and the poor. Studies comprising qualitative and quantitative methods are recommended to further explore other determinants of health care utilization.

Economic Burden of Osteoporotic Fracture of the Elderly in South Korea: A National Survey.

BACKGROUND: Osteoporotic fractures (OFs) in the elderly are common worldwide, and the predicted number of the aging population is increasing the burden of OF on health care systems. OBJECTIVES: To estimate the economic burden of OF in people older than 65 years in South Korea from a societal perspective. METHODS: National Health Insurance claim databases were used to analyze health care utilization and medical costs of OF in the Korean population (49 million). We identified medical claims records with a diagnosis of OF and estimated the costs from 2007 to 2011. RESULTS: From 2007 to 2011, there were 244,798 patients with at least one medical insurance claim related to OF. Most patients had a single fracture (80%), whereas 20% of all patients had two or more. For fracture sites, vertebral fracture accounted for 75.6% of all fractures, followed by hip and wrist fractures. The societal cost of OF increased annually, from US $88.8 million in 2007 to US $149.3 million in 2011. Among the entire cost, the direct medical cost was US $134.9 million in 2011, which includes the cost of treatment (US $91.2 million) and long-term care (US $48.1 million). The direct nonmedical cost was US $9.9 million in 2011. Costs associated with morbidity and mortality of OF were excluded. CONCLUSIONS: The economic burden associated with OF in elderly is expected to rise with the predicted increase in life expectancy and the number of elderly in South Korea. Therefore, effective management of the disease is necessary to reduce the growth in the economic burden of OF.

Treatment strategies for stage IB cervical cancer: A cost-effectiveness analysis from Korean, Canadian and U.S. perspectives.

OBJECTIVES: To assess the cost-effectiveness of two commonly used strategies and an alternative triage strategy for patients with Stage IB cervical cancer in the U.S., Canada, and Korea. METHODS: A Markov state-transition model was constructed to compare three strategies: (1) radical hysterectomy followed by tailored adjuvant therapy (primary surgery), (2) primary chemoradiation, and (3) an MRI-based triage strategy, in which patients without risk factors in preoperative MRI undergo primary surgery and those with risk factors undergo primary chemoradiation. All relevant literature was identified to extract the probability data. Cost data were calculated from the perspective of U.S., Canadian, and Korean payers. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Cost-effectiveness ratios were analyzed separately using data from each country. RESULTS: Base case analysis showed that the triage strategy was the most cost-effective of the three strategies in all countries at usual willingness-to-pay threshold (Korea: $30,000 per quality-adjusted life year (QALY), Canada and US: $100,000 per QALY). Monte Carlo simulation acceptability curves from Korea indicated that at a willingness-to-pay threshold of $30,000/QALY, triage strategy was the treatment of choice in 71% of simulations. Monte Carlo simulation acceptability curves from US and Canada indicated that at a willingness-to-pay threshold of $100,000/QALY, triage strategy was the treatment of choice in more than half of simulations. CONCLUSIONS: An MRI-based triage strategy was shown to be more cost-effective than primary surgery or primary chemoradiation in the US, Canada, and Korea.

The economic burden of chronic obstructive pulmonary disease from 2004 to 2013.

OBJECTIVES: This study examines the epidemiology and economic impact of chronic obstructive pulmonary disease (COPD) at a nationwide level in South Korea. METHODS: This retrospective analysis used the societal cost-of-illness framework, consisting of direct medical costs, direct non-medical costs, and indirect costs. In order to analyze the societal costs of patients with COPD, this study used a data mining and a macro-costing method on data from a South Korean national-level health survey and a national health insurance claims database from 2004-2013. RESULTS: The total societal cost of COPD in 2013 was estimated to be $439.9 million for 1,419,914 patients. The direct medical cost for COPD was $214.3 million, which included a hospitalization cost of $96.3 million, an outpatient cost of $76.4 million, and a pharmaceutical cost of $41.6 million. The direct non-medical cost was estimated at $43.5 million. The indirect overall cost associated with the morbidity and mortality of COPD was $182.2 million in 2013. CONCLUSIONS: This study showed that COPD has a major effect on healthcare costs, particularly direct medical costs. Thus, appropriate long-term interventions are recommended to lower the economic burden of COPD in South Korea.

Factors Determining Children's Private Health Insurance Enrolment and Healthcare Utilization Patterns: Evidence From the 2008 to 2011 Health Panel Data.

OBJECTIVES: Parental socioeconomic status (SES) exerts a substantial influence on children's health. The purpose of this study was to examine factors determining children's private health insurance (PHI) enrolment and children's healthcare utilization according to PHI coverage. METHODS: Korea Health Panel data from 2011 (n=3085) was used to explore the factors determining PHI enrolment in children younger than 15 years of age. A logit model contained health status and SES variables for both children and parents. A fixed effects model identified factors influencing healthcare utilization in children aged 10 years or younger, using 2008 to 2011 panel data (n=9084). RESULTS: The factors determining children's PHI enrolment included children's age and sex and parents' educational status, employment status, and household income quintile. PHI exerted a significant effect on outpatient cost, inpatient cost, and number of admissions. Number of outpatient visits and total length of stay were not affected by PHI status. The interaction between PHI and age group increased outpatient cost significantly. CONCLUSIONS: Children's PHI enrolment was influenced by parents' SES, while healthcare utilization was affected by health and disability status. Therefore, the results of this study suggest disparities in healthcare utilization according to PHI enrollment.

Cost-effectiveness of para-aortic lymphadenectomy before chemoradiotherapy in locally advanced cervical cancer.

OBJECTIVE: To evaluate the cost-effectiveness of nodal staging surgery before chemoradiotherapy (CRT) for locally advanced cervical cancer in the era of positron emission tomography/computed tomography (PET/CT). METHODS: A modified Markov model was constructed to evaluate the cost-effectiveness of para-aortic staging surgery before definite CRT when no uptake is recorded in the para-aortic lymph nodes (PALN) on PET/CT. Survival and complication rates were estimated based on the published literature. Cost data were obtained from the Korean Health Insurance Review and Assessment Service. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed, including estimates for the performance of PET/CT, postoperative complication rate, and varying survival rates according to the radiation field. RESULTS: We compared two strategies: strategy 1, pelvic CRT for all patients; and strategy 2, nodal staging surgery followed by extended-field CRT when PALN metastasis was found and pelvic CRT otherwise. The ICER for strategy 2 compared to strategy 1 was $19,505 per quality-adjusted life year (QALY). Under deterministic sensitivity analyses, the model was relatively sensitive to survival reduction in patients who undergo pelvic CRT alone despite having occult PALN metastasis. A probabilistic sensitivity analysis demonstrated the robustness of the case results, with a 91% probability of cost-effectiveness at the willingness-to-pay thresholds of $60,000/QALY. CONCLUSION: Nodal staging surgery before definite CRT may be cost-effective when PET/CT imaging shows no evidence of PALN metastasis. Prospective trials are warranted to transfer these results to guidelines.