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

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

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

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

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

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

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

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

Comparative Cost-Effectiveness of Tofacitinib With Continuing Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs for Active Rheumatoid Arthritis in South Korea.

INTRODUCTION: The objective of this study was to evaluate the cost-effectiveness of initiating treatment with tofacitinib and subsequently incorporating it into a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) treatment sequence and to compare the cost-effectiveness of this sequence with that of continuing csDMARDs alone in patients with active rheumatoid arthritis (RA). METHODS: A cohort-based Markov model was used to evaluate the cost-effectiveness of two tofacitinib treatment sequences compared with that of continuing the csDMARD treatment sequence over a lifetime. Of the two tofacitinib sequences, the first consisted of initial tofacitinib treatment followed by biologic DMARDs (bDMARDs) and the second consisted of csDMARD treatments followed by tofacitinib. A third treatment sequence, continuing the csDMARD treatment sequence before starting bDMARDs, was used as a comparator. Efficacy was assessed using the American College of Rheumatology (ACR) response rates (ACR 20, ACR 50, and ACR 70) after 6 months, which were converted to changes in the health assessment questionnaire-disability index (HAQ-DI) score. Utility was estimated by mapping from the HAQ-DI score, costs were analyzed from a Korean societal perspective, and outcomes were considered in terms of quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. RESULTS: The incremental cost-effectiveness ratios over a lifetime for starting with tofacitinib and incorporating tofacitinib into the csDMARD treatment sequence versus continuing csDMARDs only were US$14,537 per QALY and US$7,086 per QALY, respectively. One-way sensitivity analysis and probabilistic sensitivity analysis confirmed the robustness of these results. CONCLUSION: Starting with tofacitinib and incorporating it into a csDMARDs treatment sequence is cost-effective compared to continuing csDMARDs alone in patients with RA.

Economic burden of subsequent fracture in osteoporosis patients in South Korea.

OBJECTIVES: This study aimed to assess the economic burden of subsequent fracture in osteoporosis patients with incident fracture. METHODS: The authors conducted a retrospective cohort analysis of the South Korean national health insurance claims data. Study subjects included osteoporosis patients aged ≥50 with incident fracture (July 1, 2014-June 30, 2015). Fracture-related 1-year healthcare cost was evaluated after incident fracture for patients with and without subsequent fracture, defined as a fracture occurring within 2 years from incident fracture at a different site or at the same site after 6-months washout period. Per-patient-per-month (PPPM) cost was calculated by dividing each patient's cumulative healthcare cost until subsequent fracture with time-to-subsequent-fracture. For the patients without subsequent fracture, PPPM cost equaled 1-year monthly cost. A generalized linear model (GLM) was used to estimate the ratio of increase in healthcare cost to assess the economic impact of subsequent fracture. RESULTS: A total of 73,717 osteoporosis patients with incident fracture were identified, consisting of 52.1% vertebral, 1.9% hip, and 46.0% non-vertebral-non-hip fractures. Subsequent fracture occurred in 17.9% of patients with average time-to-subsequent-fracture of 256 days. Patients with subsequent fracture had significantly higher 1-year healthcare cost after incident fracture than those without subsequent fracture ($4,307 vs $1,721) and the difference was greater in PPPM cost ($930 vs $141). GLM analysis showed that having subsequent fracture increased both 1-year healthcare cost and PPPM cost by 1.91-fold (95% CI = 1.87-1.95) and 6.14-fold (95% CI = 5.99-6.28), respectively. CONCLUSIONS: Subsequent fracture imposes a substantial burden on osteoporosis patients and, therefore, more efforts are needed for preventing subsequent fracture among osteoporosis patients.

A disposable amperometric dual-sensor for the detection of hemoglobin and glycated hemoglobin in a finger prick blood sample.

A disposable microfluidic amperometric dual-sensor was developed for the detection of glycated hemoglobin (HbA1C) and total hemoglobin (Hb), separately, in a finger prick blood sample. The accurate level of total Hb was determined through the measurements of the cathodic currents of total Hb catalyzed by a toluidine blue O (TBO)-modified working electrode. Subsequently, after washing unbound Hb in the fluidic channel of dual sensor with PBS, the cathodic current by only HbA1C captured on aptamer was monitored using another aptamer/TBO-modified working electrode in the channel. To modify the sensor probe, poly(2,2´:5´,5″-terthiophene-3´-p-benzoic acid) and a multi-wall carbon nanotube (MWCNT) composite layer (pTBA@MWCNT) was electropolymerized on a screen printed carbon electrode (SPCE), followed by immobilization of TBO for the total Hb probe and aptamer/TBO for the HbA1C probe, respectively. The characterization of each sensor surface was performed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), quartz crystal microbalance (QCM), field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). The experimental conditions affecting the analytical signal were optimized in terms of the amount of TBO, pH, temperature, binding time, applied potential, and the content ratio of monomer and MWCNT. The dynamic ranges of Hb and HbA1C were from 0.1 to 10µM and from 0.006 to 0.74µM, with detection limits of 82(±4.2)nM and 3.7(±0.8)nM, respectively. The reliability of the proposed microfluidic dual-sensor for a finger prick blood sample (1µL) was evaluated in parallel with a conventional method (HPLC) for point-of-care analysis.