The Primary Process and Key Concepts of Economic Evaluation in Healthcare.

Economic evaluations in the healthcare are used to assess economic efficiency of pharmaceuticals and medical interventions such as diagnoses and medical procedures. This study introduces the main concepts of economic evaluation across its key steps: planning, outcome and cost calculation, modeling, cost-effectiveness results, uncertainty analysis, and decision-making. When planning an economic evaluation, we determine the study population, intervention, comparators, perspectives, time horizon, discount rates, and type of economic evaluation. In healthcare economic evaluations, outcomes include changes in mortality, the survival rate, life years, and quality-adjusted life years, while costs include medical, non-medical, and productivity costs. Model-based economic evaluations, including decision tree and Markov models, are mainly used to calculate the total costs and total effects. In cost-effectiveness or costutility analyses, cost-effectiveness is evaluated using the incremental cost-effectiveness ratio, which is the additional cost per one additional unit of effectiveness gained by an intervention compared with a comparator. All outcomes have uncertainties owing to limited evidence, diverse methodologies, and unexplained variation. Thus, researchers should review these uncertainties and confirm their robustness. We hope to contribute to the establishment and dissemination of economic evaluation methodologies that reflect Korean clinical and research environment and ultimately improve the rationality of healthcare policies.

Prevalence and socioeconomic burden of diabetes mellitus in South Korean adults: a population-based study using administrative data.

BACKGROUND: Diabetes leads to severe complications and imposes health and financial burdens on the society. However, currently existing domestic public health studies of diabetes in South Korea mainly focus on prevalence, and data on the nationwide burden of diabetes in South Korea are lacking. The study aimed to estimate the prevalence and economic burden of diabetes imposed on the South Korean society. METHODS: A prevalence-based cost-of-illness study was conducted using the Korean national claims database. Adult diabetic patients were defined as those aged ≥20 years with claim records containing diagnostic codes for diabetes (E10-E14) during at least two outpatient visits or one hospitalization. Direct costs included medical costs for the diagnosis and treatment of diabetes and transportation costs. Indirect costs included productivity loss costs due to morbidity and premature death and caregivers' costs. Subgroup analyses were conducted according to the type of diabetes, age (< 65 vs. ≥65), diabetes medication, experience of hospitalization, and presence of diabetic complications or related comorbidities. RESULTS: A total of 4,472,133 patients were diagnosed with diabetes in Korea in 2017. The average annual prevalence of diabetes was estimated at 10.7%. The diabetes-related economic burden was USD 18,293 million, with an average per capita cost of USD 4090 in 2019. Medical costs accounted for the biggest portion of the total cost (69.5%), followed by productivity loss costs (17.9%), caregivers' costs (10.2%), and transportation costs (2.4%). According to subgroup analyses, type 2 diabetes, presence of diabetic complications or related comorbidities, diabetes medication, and hospitalization represented the biggest portion of the economic burden for diabetes. As the number of complications increased from one to three or more, the per capita cost increased from USD 3991 to USD 11,965. In inpatient settings, the per capita cost was ~ 10.8 times higher than that of outpatient settings. CONCLUSIONS: South Korea has a slightly high prevalence and economic burden of diabetes. These findings highlight the need for effective strategies to manage diabetic patients and suggest that policy makers allocate more health care resources to diabetes. This is the first study on this topic, conducted using a nationally representative claims database in South Korea.

Cost-effectiveness of Bariatric Surgery for People with Morbid Obesity in South Korea.

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of bariatric surgery (BS) compared to non-surgical treatment (NST) in Korean people with morbid obesity according to comorbidities and body mass index (BMI) severity. METHODS: The target cohort was people with morbid obesity, defined as BMI of ≥ 35 kg/m2, or obese people with BMI of 30-34.9 kg/m2 having obesity-related comorbidities. A decision-tree model for 1-year obesity treatment and Markov model for the rest of life were used. In the decision-tree model, the comorbidity remission rate and BMI change after 1-year treatment were decided based on a prospective clinical trial. In the Markov model, the transition probabilities were calculated considering the BMI level and age. The starting age of 20 years, a cycle length of 1 year, a time horizon of 80 years, and a 5% discount rate were applied for the base case from the healthcare system perspective. RESULTS: In the base case, BS improved quality-adjusted life years (QALYs) and was the cost-effective option in total cohort (incremental cost-effectiveness ratio of BS vs. NST was 674 USD/QALY). It was shown to be cost-effective in all subgroup analyses based on BMI level. In particular, BS was a dominant alternative for the subgroup with basal BMI of 35.0-37.4 kg/m2. Various sensitivity analyses showed the robustness of results indicating the cost-effectiveness of BS. CONCLUSION: BS at BMI of > 30 kg/m2 was more effective than NST for a reduction in BMI and remission of obesity-related comorbidities and was cost-effective in Korea.

The incremental economic burden of heart failure: A population-based investigation from South Korea.

BACKGROUND: The prevalence of heart failure (HF) and its economic burden are increasing with age of the South Korean population. This study aimed to assess the economic impact of HF from the societal perspective. METHODS: A prevalence-based, incremental cost-of-patient study was performed to estimate the cost ratio between patients with HF and those without HF based on the claims database of the national health insurance in South Korea. We defined adult HF patients as those aged ≥19 years who had at least one insurance claim record with a primary or secondary diagnosis of HF. Age- and gender-matched controls were defined using a 1:4 greedy matching method. Costs were estimated by including medical costs for insurance-covered and non-covered services, transportation costs, caregiver's cost, and time costs of patients. The ratio of costs between patients with HF and those without HF was adjusted for age, gender, and type of universal health security program in the multivariate regression model. RESULTS: The average annual per-capita cost was estimated to be $6,601 for patients with HF (n = 14,252), which is about 3.38 (95% confidence interval [CI]: 3.31-3.46) times higher than that for patients without HF (n = 1,116,882) and 1.64 (95% CI: 1.59-1.70) times higher than that for the age- and gender-matched patients without HF (n = 57,008). In the multivariate regression model, the annual per-capita total costs were 1.98-fold (95% CI: 1.94-2.02) statistically higher for patients with HF than for patients without HF after adjustment for age, gender, and type of universal health security program. CONCLUSIONS: This study demonstrates a significant incremental burden of HF. Given that the prevalence of HF is expected to increase with an increase in the aging population, the national economic burden is expected to be substantial in the future. Thus, greater emphasis on the prevention and treatment of HF is warranted.

Comparison of screening strategies for prevalent vertebral fractures in South Korea: vertebral fracture assessment vs. spine radiography.

BACKGROUND: Vertebral Fracture Assessment (VFA) is a useful tool to detect the vertebral fracture (VF) with low cost and radiation exposure. We aimed to compare screening strategies including VFA and spine radiography (X-ray) for detecting VF in terms of clinical effectiveness, cost and radiation exposure. METHODS: Three screening strategies: 1) X-ray following VFA, 2) VFA only, and 3) X-ray only were compared using a Markov model based on administrative data from South Korea in a population aged ≥50 years. We compared the incidence of new VFs, cost-effectiveness of reducing new VFs and radiation exposure in each strategy. RESULTS: The incidence of new VFs was reduced in all screening strategies compared to no screening: 29.4% for women and 12.5% for men in both X-ray following the VFA and VFA only strategies and 35% for women and 17.5% for men in the X-ray only strategy. The X-ray following VFA strategy had the lowest cost, followed by the X-ray only, and VFA only strategies. The radiation doses for X-ray only were 2,647-2,989 µSv and 3,253-3,398 µSv higher than in the X-ray following VFA and VFA only strategies. The new VF prevention effect was greater in women, and more prominent in older people (women ≥ 70, men ≥ 80) than people ≥ 50 years. CONCLUSIONS: The X-ray following VFA strategy is a cost-effective option for screening prevalent VF to prevent new VF in people aged ≥50 years due to its high effectiveness, lowest cost, and least radiation exposure.

Differential Gene Expression (DEX) and Alternative Splicing Events (ASE) for Temporal Dynamic Processes Using HMMs and Hierarchical Bayesian Modeling Approaches.

In gene expression profile, data analysis pipeline is categorized into four levels, major downstream tasks, i.e., (1) identification of differential expression; (2) clustering co-expression patterns; (3) classification of subtypes of samples; and (4) detection of genetic regulatory networks, are performed posterior to preprocessing procedure such as normalization techniques. To be more specific, temporal dynamic gene expression data has its inherent feature, namely, two neighboring time points (previous and current state) are highly correlated with each other, compared to static expression data which samples are assumed as independent individuals. In this chapter, we demonstrate how HMMs and hierarchical Bayesian modeling methods capture the horizontal time dependency structures in time series expression profiles by focusing on the identification of differential expression. In addition, those differential expression genes and transcript variant isoforms over time detected in core prerequisite steps can be generally further applied in detection of genetic regulatory networks to comprehensively uncover dynamic repertoires in the aspects of system biology as the coupled framework.

Prevalence and socio-economic burden of heart failure in an aging society of South Korea.

BACKGROUND: Heart failure (HF) is one of the leading causes of morbidity and mortality in South Korea. With the rapidly aging population in the country, the prevalence of HF and its associated costs are expected to rise continuously. This study was carried out to estimate the prevalence and economic burden of HF in order to understand its impact on our society. METHODS: A prevalence-based, cost-of-illness study was conducted using the 2014 Health Insurance Review and Assessment Service-National Patients Sample (HIRA-NPS) data. Adult HF patients were defined as those aged ≥19 years who had at least one insurance claim record with a primary or secondary diagnosis of HF (ICD-10 codes of I11.0, I13.0, I13.2, and I50.x). The costs consist of direct costs (i.e., medical and non-medical costs) and indirect costs (i.e., productivity loss cost due to morbidity and premature death). Subgroup analyses were conducted by age group, history of HF hospitalization, and type of universal health security program enrolled in. RESULTS: A total of 475,019 adults were identified to have HF in 2014. The estimated prevalence rate of HF was 12.4 persons per 1,000 adults. According to the base cases and the extended definition of the cases, the annual economic burden of HF from a societal perspective ranges from USD 1,414.0 to 1,560.5 for individual patients, and from USD 752.8 million to 1,085.6 million for the country. A high percentage (68.5 %) of this socioeconomic burden consist of medical costs, followed by caregiver's cost (13.2 %), productivity loss costs due to premature death (10.8 %) and morbidity (4.2 %), and transportation costs (3.4 %). The HF patients with prior hospitalization due to HF annually spent 9.7 times more for National-Health-Insurance-covered medical costs compared to HF patients who were not previously hospitalized. CONCLUSIONS: In the present study, HF patients who were older and had a history of prior hospitalization for HF as well as an indigent status were shown at high risk of spending more for healthcare to treat their HF. An effective disease management protocol should be employed to target this patient group.

In-depth investigation for prescribing trends of benzodiazepines in South Korea.

This study aimed to investigate national prescription trends of benzodiazepines (BZD) for adults between 2007 and 2011 using Health Insurance Review and Assessment Service (HIRA) database in South Korea. Data analysis was performed by claim unit or patient unit. For the analysis of patient unit, each claim was merged by the same patient. Defined daily dose (DDD) was used to analyze the data in terms of dose and periods of BZD prescription. We identified a total of 22,361,449 adult patients who had BZD prescription at least once in 1,989,263 claims during 5 years. The average national BZD prescription prevalence for 1 year was 23.7%, 7.9%, 4.7%, and 3.2% of >= 1 day supply, >= 30 days supply, >= 90 days supply, and >= 180 days supply, respectively. The trends for 5 years were very similar. Among study population, 87.7% visited only non-psychiatric departments and the most frequent indication was gastrointestinal related diseases. BZD consumption expressed as DDDs per 1,000 inhabitants per day was 109.2. BZD consumption tended to be ~ 4 x higher in elderly than that of non-elderly (268.6 vs. 60.0 in male and 367.7 vs. 90.9 in female). Our study indicated the possibilities for inappropriate prescription of BZD, and the limitation policy on continuous prescription over 30 days supply did not seem to be effective. The effective interventions including an educational program for appropriate prescription of BZD should be considered.

Economic evaluation of single-tooth replacement: dental implant versus fixed partial denture.

PURPOSE: This study assessed the cost-effectiveness from a societal perspective of a dental implant compared with a three-unit tooth-supported fixed partial denture (FPD) for the replacement of a single tooth in 2010. MATERIALS AND METHODS: A decision tree was developed to estimate cost-effectiveness over a 10-year period. The survival rates of single-tooth implants and FPDs were extracted from a meta-analysis of single-arm studies. Medical costs included initial treatment costs, maintenance costs, and costs to treat complications. Patient surveys were used to obtain the costs of the initial single-tooth implant or FPD. Maintenance costs and costs to treat complications were based on surveys of seven clinical experts at dental clinics or hospitals. Transportation costs were calculated based on the number of visits for implant or FPD treatment. Patient time costs were estimated using the number of visits and time required, hourly wage, and employment rate. Future costs were discounted by 5% to convert to present values. RESULTS: The results of a 10-year period model showed that a single dental implant cost US $261 (clinic) to $342 (hospital) more than an FPD and had an average survival rate that was 10.4% higher. The incremental cost-effectiveness ratio was $2,514 in a clinic and $3,290 in a hospital for a prosthesis in situ for 10 years. The sensitivity analysis showed that initial treatment costs and survival rate influenced the cost-effectiveness. If the cost of an implant were reduced to 80% of the current cost, the implant would become the dominant intervention. CONCLUSION: Although the level of evidence for effectiveness is low, and some aspects of single-tooth implants or FPDs, such as satisfaction, were not considered, this study will help patients requiring single-tooth replacement to choose the best treatment option.

The burden of nosocomial staphylococcus aureus bloodstream infection in South Korea: a prospective hospital-based nationwide study.

BACKGROUND: We estimated the nationwide burden of nosocomial S. aureus bloodstream infection (SA-BSI), a major cause of nosocomial infection, in South Korea. METHODS: To evaluate the nationwide incidence of nosocomial SA-BSI, cases of SA-BSI were prospectively collected from 22 hospitals with over 500 beds over 4?months. Data on patient-days were obtained from a national health insurance database containing the claims data for all healthcare facilities in South Korea. The additional cost of SA-BSI was estimated through a matched case?control study. The economic burden was calculated from the sum of the medical costs, the costs of caregiving and loss of productivity. RESULTS: Three hundred and thirty nine cases of nosocomial SA-BSI were included in the study: 254 cases of methicillin-resistant SA-BSI (MRSA-BSI) and 85 cases of methicillin-susceptible SA-BSI (MSSA-BSI). Death related to BSI occurred in 81 cases (31.9%) of MRSA-BSI and 12 cases (14.1%) of MSSA-BSI. The estimated incidence of nosocomial MRSA-BSI was 0.12/1,000 patient-days and that of nosocomial MSSA-BSI, 0.04/1,000 patient-days. The estimated annual cases of nosocomial BSI were 2,946 for MRSA and 986 for MSSA in South Korea. The additional economic burden per case of nosocomial SA-BSI was US $20,494 for MRSA-BSI and $6,914 for MSSA-BSI. Total additional annual cost of nosocomial SA-BSI was $67,192,559. CONCLUSION: In view of the burden of nosocomial SA-BSI, a national strategy for reducing nosocomial SA-BSI is urgently needed in South Korea.

Bariatric surgery for the treatment of severely obese patients in South Korea--is it cost effective?

BACKGROUND: In South Korea, the number of severely obese patients has increased. An economic study comparing bariatric surgery with nonsurgical interventions has not been published for Asia. OBJECTIVES: This study was conducted to evaluate the cost effectiveness of bariatric surgery as compared to nonsurgical interventions for severe obese Korean people. METHODS: We used the Markov model to compare the lifetime expected costs and quality-adjusted life years (QALYs) between bariatric surgery and nonsurgical interventions from Korean Healthcare system perspectives. Our target cohort consisted of severe obese people defined as having a body mass index of 30-<40 kg/m(2) in South Korea. The starting age of the cohort was 30 years old, and the cycle length was 1 year. Nonsurgical interventions included a physician visit, exercise, diet, and pharmacotherapy. A discount of 5 % was applied in cost and QALY. The incremental cost-effectiveness ratio (ICER) of bariatric surgery compared to nonsurgery interventions was calculated. RESULTS: The cost-utility analysis study indicated that bariatric surgery had US$1,522 incremental costs and 0.86 incremental QALYs as compared to nonsurgical interventions. Through the base case analysis, ICER was US$1,771/QALY. The sensitivity analyses were performed using a variety of assumptions, and the robustness of the study results was also demonstrated. CONCLUSION: The study indicated that bariatric surgery was a cost-effective alternative to nonsurgical interventions over a lifetime, providing substantial lifetime benefits for severely obese Korean people.

Time series expression analyses using RNA-seq: a statistical approach.

RNA-seq is becoming the de facto standard approach for transcriptome analysis with ever-reducing cost. It has considerable advantages over conventional technologies (microarrays) because it allows for direct identification and quantification of transcripts. Many time series RNA-seq datasets have been collected to study the dynamic regulations of transcripts. However, statistically rigorous and computationally efficient methods are needed to explore the time-dependent changes of gene expression in biological systems. These methods should explicitly account for the dependencies of expression patterns across time points. Here, we discuss several methods that can be applied to model timecourse RNA-seq data, including statistical evolutionary trajectory index (SETI), autoregressive time-lagged regression (AR(1)), and hidden Markov model (HMM) approaches. We use three real datasets and simulation studies to demonstrate the utility of these dynamic methods in temporal analysis.

Analysis and Exposure Assessment of Perchlorate in Korean Dairy Products with LC-MS/MS.

OBJECTIVES: Perchlorate is an emerging contaminant that is found everywhere, including various foods. Perchlorate is known to disturb the production of thyroid hormones and leads to mental disorders in fetuses and infants, as well as metabolic problems in adults. In this study, we attempted to establish an LC-MS/MS method for measuring perchlorate in dairy products and used this developed method to investigate perchlorate levels in Korean milk and yogurt samples. METHODS: The developed method of perchlorate analysis requires a shaker and 1% acetic acid/acetonitrile as the extracting solvent. Briefly, the samples were extracted and then centrifuged (4000 rpm, 1hour), and the supernatant was then passed through a Envi™ Carb SPE cartridge that had been prewashed sequentially with 6 mL of acetonitrile and 6 mL of 1% acetic acid in water. The final volume of the sample extract was adjusted to 40 mL with reagent water and the final sample was filtered through a 0.20-µm pore size PTFE (Polytetrafluoroethylene) syringe filter prior to LC-MS/MS. RESULTS: The average levels of perchlorate in milk and yogurt samples were 5.63 ± 3.49 µg/L and 3.65 ± 2.42 µg/L, respectively. The perchlorate levels observed in milk samples in this study were similar to those reported from China, Japan, and the United States. CONCLUSIONS: The exposure of Koreans to perchlorate through the consumption of dairy products was calculated based on the results of this study. For all age groups, the calculated exposure to perchlorate was below the reference of dose (0.7 µg/kg-day) proposed by the National Academy of Science, USA, but the perchlorate exposure of children was higher than that of adults. Therefore, further investigation of perchlorate in other food samples is needed to enable a more exact assessment of exposure of children to perchlorate.