Critical Examination of Modeling Approaches Used in Economic Evaluations of First-Line Treatments for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: A Systematic Literature Review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. NSCLC harboring an EGFR mutation has a dedicated treatment pathway, with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy often being the therapy of choice. OBJECTIVE: The aim of this study was to systemically review and summarize economic models of first-line treatments used for locally advanced or metastatic NSCLC harboring EGFR mutations, as well as to identify areas for improvement for future models. METHODS: Literature searches were conducted via Ovid in PubMed, MEDLINE, MEDLINE In-Process, Embase, Evidence-Based Medicine Reviews: Health Technology Assessment, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database, and EconLit. An initial search was conducted on 19 December 2022 and updated on 11 April 2023. Studies were selected according to predefined criteria using the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework. RESULTS: Sixty-seven articles were included in the review, representing 59 unique studies. The majority of included models were cost-utility analyses (n = 52), with the remaining studies being cost-effectiveness analyses (n = 4) and a cost-minimization analysis (n = 1). Two studies incorporated both a cost-utility and cost-minimization analysis. Although the model structure across studies was consistently reported, justification for this choice was often lacking. CONCLUSIONS: Although the reporting of economic models in NSCLC harboring EGFR mutations is generally good, many of these studies lacked sufficient reporting of justification for structural choices, performing extensive sensitivity analyses and validation in economic evaluations. In resolving such gaps, the validity of future models can be increased to guide healthcare decision making in rare indications.

Economic evaluation of toripalimab combined with chemotherapy in the treatment of non-small cell lung cancer.

Background and objective: The CHOICE-01 trial showed that toripalimab plus chemotherapy achieved satisfactory outcomes compared with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who were negative for driver genes, but the economics of this regimen is unclear. Therefore, this study aimed to evaluate the cost-effectiveness of toripalimab in combination with chemotherapy in advanced NSCLC with negative driver genes from the perspective of the Chinese healthcare system. Materials and methods: A three-state partitioned survival model was developed to simulate the costs and outcomes associated with adding toripalimab to first-line chemotherapy. The clinical data in the model came from the CHOICE-01 trial, only direct medical costs were included, and utility values were referred to the literature. Four models were applied to explore the differences in the results of fitting and extrapolating K-M curves from different models, and cost-effectiveness subgroup analysis was performed. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the impact of parameter uncertainty on the model. Results: The baseline analysis showed that toripalimab coupled with chemotherapy cost $21,052 more than chemotherapy ($43,197 vs. $22,145) and also gained 0.71 QALYs more (1.75 QALYs vs. 1.03 QALYs), with an ICER of $29,478/QALYs. At the current willingness-to-pay threshold ($35,108/QALY), the extra cost was well worth it. The results of fitting and extrapolating the survival curves using other models were consistent with the results of the standard parametric model. Subgroup analysis demonstrated that the addition of toripalimab to chemotherapy was economical. Sensitivity analysis showed that the utility values of PD and PFS stages had the greatest impact on the model. Conclusion: From the viewpoint of the Chinese healthcare system, toripalimab combined with chemotherapy in the treatment of advanced NSCLC with negative driver genes was likely to be cost-effective compared with chemotherapy.

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.

Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain.

BACKGROUND: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. METHODS: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. RESULTS: A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. CONCLUSIONS: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

Trends in treatment patterns and survival outcomes in advanced non-small cell lung cancer: a Canadian population-based real-world analysis.

BACKGROUND: As part of the multi-country I-O Optimise research initiative, this population-based study evaluated real-world treatment patterns and overall survival (OS) in patients treated for advanced non-small cell lung cancer (NSCLC) before and after public reimbursement of immuno-oncology (I-O) therapies in Alberta province, Canada. METHODS: This study used data from the Oncology Outcomes (O2) database, which holds information for ~ 4.5 million residents of Alberta. Eligible patients were adults newly diagnosed with NSCLC between January 2010 and December 2017 and receiving first-line therapy for advanced NSCLC (stage IIIB or IV) either in January 2010-March 2016 (pre-I-O period) or April 2016-June 2019 (post-I-O period). Time periods were based on the first public reimbursement of I-O therapy in Alberta (April 2017), with a built-in 1-year lag time before this date to allow progression to second-line therapy, for which the I-O therapy was indicated. Kaplan-Meier methods were used to estimate OS. RESULTS: Of 2244 analyzed patients, 1501 (66.9%) and 743 (33.1%) received first-line treatment in the pre-I-O and post-I-O periods, respectively. Between the pre-I-O and post-I-O periods, proportions of patients receiving chemotherapy decreased, with parallel increases in proportions receiving I-O therapies in both the first-line (from < 0.5% to 17%) and second-line (from 8% to 47%) settings. Increased use of I-O therapies in the post-I-O period was observed in subgroups with non-squamous (first line, 15%; second line, 39%) and squamous (first line, 25%; second line, 65%) histology. First-line use of tyrosine kinase inhibitors also increased among patients with non-squamous histology (from 26% to 30%). In parallel with these evolving treatment patterns, median OS increased from 10.2 to 12.1 months for all patients (P < 0.001), from 11.8 to 13.7 months for patients with non-squamous histology (P = 0.022) and from 7.8 to 9.4 months for patients with squamous histology (P = 0.215). CONCLUSIONS: Following public reimbursement, there was a rapid and profound adoption of I-O therapies for advanced NSCLC in Alberta, Canada. In addition, OS outcomes were significantly improved for patients treated in the post-I-O versus pre-I-O periods. These data lend support to the emerging body of evidence for the potential real-world benefits of I-O therapies for treatment of patients with advanced NSCLC.

Trends in Prices of Drugs Used to Treat Metastatic Non-Small Cell Lung Cancer in the US From 2015 to 2020.

Importance: Oncology drug prices are a determinant of health disparities in the US and worldwide. Several new therapeutic agents for non-small cell lung cancer (NSCLC) have become available on the US market over the past decade. Although increased competition typically produces lower prices, competition among brand-name oncology drugs has not resulted in lower prices. Objective: To assess price changes in class-specific brand-name medications used to treat metastatic NSCLC in the US from 2015 to 2020. Design, Setting, and Participants: This cross-sectional study, conducted from August 13, 2015, to August 13, 2020, used data from the Micromedex Red Book and Medi-Span Price Rx databases. The study sample was limited to 17 brand-name medications used to treat metastatic NSCLC that were available for purchase before January 1, 2019. Main Outcomes and Measures: The main outcomes were trends over time in average wholesale prices and wholesale acquisition cost unit prices and the correlation in price among the multiple brand-name medications within each therapeutic class (immune checkpoint inhibitors, epidermal growth factor receptor inhibitors, anaplastic lymphoma kinase inhibitors, ROS1 inhibitors, BRAF inhibitors, and MEK inhibitors), measured using the Pearson correlation coefficient. The compounded annual growth rates of different medication costs were compared with the annual inflation rate and the consumer price index for prescription drugs. Results: For all drug classes, the Pearson correlation coefficient approached 1.0, indicating an increase in drug list prices despite within-class drug competition. The median Pearson correlation coefficient values were 0.964 (range, 0.951-0.994) for immune checkpoint inhibitors, 0.898 (range, 0.665-0.950) for epidermal growth factor receptor inhibitors, 0.999 (range, 0.982-0.999) for anaplastic lymphoma kinase inhibitors, and 0.999 for BRAF and MEK inhibitors. The median compounded annual growth rates for most drug costs were higher than the annual inflation rate and consumer price index for prescription drugs: 1.81% (range, 1.29%-2.13%) for immune checkpoint inhibitors, 2.56% (range, 2.38%-5.26%) for epidermal growth factor receptor inhibitors, 2.46% (range, 1.75%-4.66%) for anaplastic lymphoma kinase and ROS1 inhibitors, and 3.06% (range, 0%-3.06%) for BRAF and MEK inhibitors. Conclusions and Relevance: In this cross-sectional study, prices of brand-name medications for treatment of NSCLC increased in the US from 2015 to 2020 without evidence of price competition, raising concern about the affordability of promising oncology drugs. These findings suggest that drug pricing reform is needed.

Cost-effectiveness and health impact of lung cancer screening with low-dose computed tomography for never smokers in Japan and the United States: a modelling study.

BACKGROUND: Never smokers in Asia have a higher incidence of lung cancer than in Europe and North America. We aimed to assess the cost-effectiveness of lung cancer screening with low-dose computed tomography (LDCT) for never smokers in Japan and the United States. METHODS: We developed a state-transition model for three strategies: LDCT, chest X-ray (CXR), and no screening, using a healthcare payer perspective over a lifetime horizon. Sensitivity analyses were also performed. Main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios (ICERs), and deaths from lung cancer. The willingness-to-pay level was US$100,000 per QALY gained. RESULTS: LDCT yielded the greatest benefits with the lowest cost in Japan, but the ICERs of LDCT compared with CXR were US$3,001,304 per QALY gained for American men and US$2,097,969 per QALY gained for American women. Cost-effectiveness was sensitive to the incidence of lung cancer. Probabilistic sensitivity analyses demonstrated that LDCT was cost-effective 99.3-99.7% for Japanese, no screening was cost-effective 77.7% for American men, and CXR was cost-effective 93.2% for American women. Compared with CXR, LDCT has the cumulative lifetime potential for 60-year-old Japanese to save US$117 billion, increase 2,339,349 QALYs and 3,020,102 LYs, and reduce 224,749 deaths, and the potential for 60-year-old Americans to cost US$120 billion, increase 48,651 QALYs and 67,988 LYs, and reduce 2,309 deaths. CONCLUSIONS: This modelling study suggests that LDCT screening for never smokers has the greatest benefits and cost savings in Japan, but is not cost-effective in the United States. Assessing the risk of lung cancer in never smokers is important for introducing population-based LDCT screening.

Patterns of Medical Care Cost by Service Type for Patients With Recurrent and De Novo Advanced Cancer.

OBJECTIVES: There is limited knowledge about the cost patterns of patients who receive a diagnosis of de novo and recurrent advanced cancers in the United States. METHODS: Data on patients who received a diagnosis of de novo stage IV or recurrent breast, colorectal, or lung cancer between 2000 and 2012 from 3 integrated health systems were used to estimate average annual costs for total, ambulatory, inpatient, medication, and other services during (1) 12 months preceding de novo or recurrent diagnosis (preindex) and (2) diagnosis month through 11 months after (postindex), from the payer perspective. Generalized linear regression models estimated costs adjusting for patient and clinical factors. RESULTS: Patients who developed a recurrence <1 year after their initial cancer diagnosis had significantly higher total costs in the preindex period than those with recurrence ≥1 year after initial diagnosis and those with de novo stage IV disease across all cancers (all P < .05). Patients with de novo stage IV breast and colorectal cancer had significantly higher total costs in the postindex period than patients with cancer recurrent in <1 year and ≥1 year (all P < .05), respectively. Patients in de novo stage IV and those with recurrence in ≥1 year experienced significantly higher postindex costs than the preindex period (all P < .001). CONCLUSIONS: Our findings reveal distinct cost patterns between patients with de novo stage IV, recurrent <1-year, and recurrent ≥1-year cancer, suggesting unique care trajectories that may influence resource use and planning. Future cost studies among patients with advanced cancer should account for de novo versus recurrent diagnoses and timing of recurrence to obtain estimates that accurately reflect these care pattern complexities.

Cost-effectiveness of carbon-ion radiotherapy versus stereotactic body radiotherapy for non-small-cell lung cancer.

Carbon-ion radiotherapy (CIRT) for clinical stage I non-small-cell lung cancer (NSCLC) is used as an advanced medical treatment regimen in Japan. Carbon-ion radiotherapy reportedly aids in achieving excellent treatment outcomes, despite its high medical cost. We aimed to compare CIRT with stereotactic body radiotherapy (SBRT) in terms of cost-effectiveness for treating clinical stage I NSCLC. Data of patients with clinical stage I NSCLC treated with CIRT or SBRT at Gunma University between 2010 and 2015 were analyzed. The CIRT and SBRT groups included 62 and 27 patients, respectively. After propensity-score matching, both groups comprised 15 patients. Life year (LY) was used as an indicator of outcome. The CIRT technical fee was 3 140 000 JPY. There was no technical fee for the second CIRT carried out on the same organ within 2 years. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental cost by the incremental LY for 5 years after treatment. Sensitivity analysis was applied to evaluate the impact of LY or costs of each group on ICER. The ICERs were 7 491 017 JPY/LY and 3 708 330 JPY/LY for all patients and matched patients, respectively. Hospitalization and examination costs were significantly higher in the CIRT group, and the impact of the CIRT technical costs was smaller than other costs and LY. Carbon-ion radiotherapy is a cost-effective treatment approach. However, our findings suggest that reducing excessive costs by considering the validity and necessity of examinations and hospitalizations would make CIRT a more cost-effective approach.

Health care resource utilization and costs associated with advanced or metastatic nonsmall cell lung cancer in the United States.

BACKGROUND: The treatment landscape for advanced nonsmall cell lung cancer (NSCLC) has evolved from 2015 onward, since the introduction of immune checkpoint inhibitors (ICIs). Considering this shift, there have been limited prior analyses that assess the economic burden of NSCLC within the current treatment landscape. OBJECTIVE: To present an analysis of health care resource utilization (HCRU) and costs associated with the treatment of patients with advanced or metastatic NSCLC in the United States between 2010 and 2019. METHODS: Patients with locally advanced or metastatic NSCLC who initiated first-line (1L) systemic treatment between January 1, 2010, and June 30, 2019, were included from the HealthCore Integrated Research Database using a previously developed claims-based predictive model algorithm. Mean total HCRU and costs and mean per-person-per-year (PPPY) HCRU and costs were estimated for 2 follow-up periods: the time during the entire follow-up period and the time during the 1L treatment period. Distribution of treatment classes (defined as chemotherapy, ICIs, targeted therapies, and others) were also analyzed by index year. RESULTS: 27,257 patients met the eligibility criteria and were included in the analysis. The mean duration of follow-up for all patients was 16.6 months (median 10.6 months), and the median time to discontinuation of 1L treatment was 2.8 months. The number of outpatient visits accounted for the majority of HCRU across the entire study follow-up (mean 97.7 in total and 147.1 PPPY) and for the 1L treatment period (mean 46.3 in total and 167.5 PPPY). The total mean cost across the entire study follow-up was $158,908 ($250,942 PPPY). For the 1L treatment period, the total mean cost was $72,760 ($271,590 PPPY). Total mean outpatient costs for systemic anticancer treatment were $61,797 for the entire study follow-up ($85,609 PPPY) and $27,138 during the 1L treatment period ($92,412 PPPY). Total costs increased over the study duration, which were mainly due to increasing outpatient costs for systemic therapy. In both follow-up periods, inpatient costs, other outpatient costs (nonsystemic therapy-related costs), and pharmacy costs remained relatively stable but still accounted for more than 60% of the total costs. Analysis of treatment classes over time showed that chemotherapy was the most frequently used treatment, regardless of line of therapy. A trend was observed for increased ICI use from 2015 onward. CONCLUSIONS: Despite the improvement in treatment options, a high economic burden associated with the treatment of NSCLC still exists. The total costs have been increasing, mainly driven by outpatient costs for systemic therapy, which might reflect the greater use of ICIs for advanced NSCLC. Costs for inpatient services, other outpatient services, and pharmacy services remained stable but still accounted for the majority of the economic burden. Further studies are required to assess the impact of innovative treatments on the disease management costs of advanced NSCLC. DISCLOSURES: This study was funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and Pfizer. Zhang, Liu, and Yang are employees of EMD Serono. Beachler, Dinh, and Jamal-Allial are employees of HealthCore Inc., which received funding from the healthcare business of Merck KGaA, Darmstadt, Germany, and Pfizer for the implementation of this study. Masters and Kolitsopoulos are employees of Pfizer. Lamy was an employee of the healthcare business of Merck KGaA, Darmstadt, Germany, at the time this study was conducted.

Out-of-Pocket Costs Among Patients With a New Cancer Diagnosis Enrolled in High-Deductible Health Plans vs Traditional Insurance.

Importance: The financial burden of a cancer diagnosis is increasing rapidly with advances in cancer care. Simultaneously, more individuals are enrolling in high-deductible health plans (HDHPs) vs traditional insurance than ever before. Objective: To characterize the out-of-pocket costs (OOPCs) of cancer care for individuals in HDHPs vs traditional insurance plans. Design, Setting, and Participants: This retrospective cohort study used the administrative claims data of a single national insurer in the US for 134 826 patients aged 18 to 63 years with a new diagnosis of breast, colorectal, lung, or other cancer from 2008 to 2018 with 24 months or more of continuous enrollment. Propensity score matching was performed to create comparator groups based on the presence or absence of an incident cancer diagnosis. Exposures: A new cancer diagnosis and enrollment in an HDHP vs a traditional health insurance plan. Main Outcomes and Measures: The primary outcome was OOPCs among individuals with breast, colon, lung, or all other types of cancer combined compared with those with no cancer diagnosis. A triple difference-in-differences analysis was performed to identify incremental OOPCs based on cancer diagnosis and enrollment in HDHPs vs traditional plans. Results: After propensity score matching, 134 826 patients remained in each of the cancer (73 572 women [55%]; median age, 53 years [IQR, 46-58 years]; 110 071 non-Hispanic White individuals [82%]) and noncancer (66 619 women [49%]; median age, 53 years [IQR, 46-59 years]; 105 023 non-Hispanic White individuals [78%]) cohorts. Compared with baseline costs of medical care among individuals without cancer, a breast cancer diagnosis was associated with the highest incremental OOPC ($714.68; 95% CI, $664.91-$764.45), followed by lung ($475.51; 95% CI, $340.16-$610.86), colorectal ($361.41; 95% CI, $294.34-$428.48), and all other types of cancer combined ($90.51; 95% CI, $74.22-$106.79). Based on the triple difference-in-differences analysis, compared with patients without cancer enrolled in HDHPs, those with breast cancer paid $1683.36 in additional yearly OOPCs (95% CI, $1576.66-$1790.07), those with colorectal cancer paid $1420.06 more (95% CI, $1232.31-$1607.80), those with lung cancer paid $467.25 more (95% CI, $130.13-$804.37), and those with other types of cancer paid $550.87 more (95% CI, $514.75-$586.99). Conclusions and Relevance: Patients with cancer and private insurance experienced sharp increases in OOPCs compared with those without cancer, which was amplified among those with HDHPs. These findings illustrate the degree to which HDHPs offer poorer protection than traditional insurance against unexpected health care expenses. Coupled with the increasing cost of cancer care, higher cost sharing in the form of increasing enrollment in HDHPs requires further research on the potential clinical consequences through delayed or foregone care.

Catastrophic health expenditure and its determinants in households with lung cancer patients in China: a retrospective cohort study.

BACKGROUND: Numerous studies have examined catastrophic health expenditures (CHE) worldwide, mostly focusing on general or common chronic populations, rather than particularly vulnerable groups. This study assessed the medical expenditure and compensation of lung cancer, and explored the extent and influencing factors of CHE among households with lung cancer patients in China. METHODS: During 2018-2019, a hospital-based multicenter retrospective survey was conducted in seven provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. CHE was measured according to the proportion of out-of-pocket (OOP) health payments of households on non-food expenditures. Chi-square tests and logistic regression analysis was adjusted to determine the factors that significantly influenced the likelihood of a household with lung cancer patient to incur in CHE. RESULTS: In total, 470 households with lung cancer patients were included in the analysis. Health insurance was shown to protect some households from the impact of CHE. Nonetheless, CHE incidence (78.1%) and intensity (14.02% for average distance and 22.56% for relative distance) were still relatively high among households with lung cancer patients. The incidence was lower in households covered by the Urban Employee Basic Medical Insurance (UEMBI) insurance, with higher income level and shorter disease course. CONCLUSION: More attention is needed for CHE incidence among vulnerable populations in China. Households with lung cancer patients were shown to be more likely to develop CHE. Therefore, policy makers should focus on improving the financial protection and reducing the economic burden of this disease.

Escalated grades of complications correlate with incremental costs of video-assisted thoracoscopic surgery major lung resection for lung cancer in China.

OBJECTIVE: Few studies have focused on factors associated with the incremental cost of video-assisted thoracoscopic surgery (VATS) in China. We aim to systematically classify the complications after VATS major lung resection and explore their correlation with hospital costs. METHODS: Patients with pathologically stage I-III lung cancer who underwent VATS major lung resections from January 2007 to December 2018 were included. The Thoracic Mortality and Morbidity (TM&M) Classification system was used to evaluate postoperative complications. Grade I and II complications, defined as minor complications, require no therapy or pharmacologic intervention only. Grade III and IV complications, defined as major complications, require surgical intervention or life support. Grade V results in death. A generalized linear model was used to explore the correlation of incremental hospital costs and complications, as well as other clinicopathologic parameters between 2013 and 2016. RESULTS: A total of 2881 patients were enrolled in the first part, and the minor and major complications rates were 24.3% (703 patients) and 8.3% (228 patients), respectively. Six hundred and eighty-two patients were enrolled in the second part. The complications grade II (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.05-1.2, p = 0.0005), grade III (OR 1.55, 95% CI 1.26-1.9, p < 0.0001), grades IV and V (OR 1.09, 95% CI 1.04-1.13, p = 0.0002), diffusion capacity of carbon dioxide (OR 0.998, 95% CI 0.997-1.000, p = 0.004), and duration of chest drainage (OR 1.03, 95% CI 1.02-1.04, p < 0.001) and were independent risk factors for the increase in in-hospital costs of VATS major lung resections. CONCLUSIONS: The severity of complications graded by the TM&M system was an independent risk factor for increased in-hospital costs.

Out-of-pocket medical expenses compared across five years for patients with one of five common cancers in Australia.

BACKGROUND: Patient medical out-of-pocket expenses are thought to be rising worldwide yet data describing trends over time is scant. We evaluated trends of out-of-pocket expenses for patients in Australia with one of five major cancers in the first-year after diagnosis. METHODS: Participants from the QSKIN Sun and Health prospective cohort Study with a histologically confirmed breast, colorectal, lung, melanoma, or prostate cancer diagnosed between 2011 and 2015 were included (n = 1965). Medicare claims data on out-of-pocket expenses were analysed using a two-part model adjusted for year of diagnosis, health insurance status, age and education level. Fisher price and quantity indexes were also calculated to assess prices and volumes separately. RESULTS: On average, patients with cancer diagnosed in 2015 spent 70% more out-of-pocket on direct medical expenses than those diagnosed in 2011. Out-of-pocket expenses increased significantly for patients with breast cancer (mean AU$2513 in 2011 to AU$6802 in 2015). Out-of-pocket expenses were higher overall for individuals with private health insurance. For prostate cancer, expenses increased for those without private health insurance over time (mean AU$1586 in 2011 to AU$4748 in 2014) and remained stable for those with private health insurance (AU$4397 in 2011 to AU$5623 in 2015). There were progressive increases in prices and quantities of medical services for patients with melanoma, breast and lung cancer. For all cancers, prices increased for medicines and doctor attendances but fluctuated for other medical services. CONCLUSION: Out-of-pocket expenses for patients with cancer have increased substantially over time. Such increases were more pronounced for women with breast cancer and those without private health insurance. Increased out-of-pocket expenses arose from both higher prices and higher volumes of health services but differ by cancer type. Further efforts to monitor patient out-of-pocket costs and prevent health inequities are required.

Measuring the Value Healthy Individuals Place on Generous Insurance Coverage of Severe Diseases: A Stated Preference Survey of Adults Diagnosed With and Without Lung Cancer.

OBJECTIVES: To compare the ex ante willingness to pay (WTP) of healthy individuals for generous insurance coverage of novel lung cancer treatments to the WTP for coverage of such treatment among individuals with lung cancer. METHODS: A survey was administered to 2 cohorts of US adults: (1) healthy individuals without cancer and (2) individuals diagnosed with lung cancer. A multiple random staircase survey design was used to elicit respondent WTP for coverage of novel lung cancer therapy associated with survival gains. RESULTS: Of the 84 937 healthy individuals invited, 300 completed the survey. Of the 36 249 in the lung cancer cohort invited, 250 completed the survey. Mean age by cohort was 50.0 (SD 14.6) and 48.4 (SD 16.8) years, and 55.2% and 47.2% were female, respectively. Respondents in the healthy and lung cancer cohorts were willing to pay $97.52 (95% confidence interval (CI) $89.89-$105.15) and $22 304 (95% CI $20 194-$24 414) per month, respectively, for coverage of a novel therapy providing 5-year survival of 15% versus standard-of-care therapy with a 5-year survival of 4%. After accounting for the likelihood that healthy individuals are diagnosed with lung cancer in the future, we estimated that 89.8% of the total value of new lung cancer treatments comes from the WTP healthy individuals place on generous insurance coverage. CONCLUSIONS: Total societal willingness to pay for lung cancer is much higher than conventionally thought, as most healthy individuals are risk-averse and highly value having lung cancer treatments available to them in the future.

Efficacy and cost of high-frequency IGRT in elderly stage III non-small-cell lung cancer patients.

BACKGROUND: High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). METHODS: We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods. RESULTS: Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86-1.09), ETFS (HR 1.05; 95% CI 0.93-1.18), CSS (HR 0.94; 95% CI 0.84-1.04), or OS (HR 0.95; 95% CI 0.87-1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively. CONCLUSION: hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

Assessment of health status for the purposes of benefi ts and social security services for people with lung cancer and the economic impact of this disease on social security in the Czech Republic.

BACKGROUND: The paper deals with temporary incapacity for work and newly created first, second or third degree disability in people dia-gnosed with lung cancer (dg. C34). The aim of this study was to describe the economic impacts on the budget in the Czech Republic, spent through the Czech Social Security Administration on temporary incapacity for work and newly created disability pensions due to the disease. For greater completeness of the impact on the budget of the Czech Republic, we have also provided an overview of applications for care allowance and applications for the purpose of granting a disability card. MATERIAL AND METHODS: The starting point for the evaluation was the data provided by the Czech Social Security Administration. The basic research group consisted of people with dg. C34, who applied for an invalidity pension in 2016-2019, due to first, second and third degree invalidities. The disability and temporary incapacity for work is therefore related to a group of people at working age. With the help of quantitative research using content analysis of the text, we performed data evaluation. RESULTS: We found that even though the number of people applying for a disability pension for dg. C34 is declining slightly, the expenditure on these pensions is still high. In the years 2016, 2017, 2018 and 2019, the research groups consisted of 612, 631, 576 and 543 people, respectively. CONCLUSION: The disease associated with lung cancer is not only characterized by high mortality, but is also one of the very common causes of temporary incapacity for work and new disabilities. This fact therefore contributes significantly to the economic costs of the Czech Republic.

Estimated annual prevalence, medical service utilization and direct costs of lung cancer in urban China.

BACKGROUND: Evidence-based policy making for delivering affordable lung cancer care relies on the breadth, depth and quality of knowledge of its treatment costs. This study estimates the annual prevalence, medical service utilization and direct treatment costs of lung cancer in urban China. MATERIALS AND METHODS: Using claim data from China's urban basic medical insurance between 2013 and 2016, we constructed a nationally representative sample of lung cancer patients in urban China. Weighted descriptive analyses, Poisson regressions and generalized linear modelling were used to analyse lung cancer medical service utilization and costs and their associations with patient characteristics. RESULTS: In urban China, the annual prevalence of lung cancer was 87.65/100000, with nearly 0.65% of total health expenditures of urban residents spent on lung cancer treatments. Weighted average annual total medical costs of lung cancer was RMB33.78 (US$5.36) thousand, with annual out-of-pocket costs of RMB10.26 (US$1.63) thousand. The average yearly number of lung cancer-related outpatient visits was 2.42 and inpatient admissions was 2.07, with an average cost of RMB0.75 (US$0.12) thousand for outpatients and RMB 15.67 (US$2.49) thousand for inpatients. Inpatient expenses were the major component (95%) of lung cancer medical costs, with roughly 67% of inpatient services occurring in high-level tertiary hospitals. Medical care utilization and direct medical costs were associated with sex, age and insurance status. Western medicine costs were the major contributor (39.4%) to average lung cancer-related medical costs. CONCLUSION: Lung cancer imposed a significant economic burden on China's health system and a financial cost on lung cancer sufferers and their families. Specific policies are required to efficiently allocate health resources, contain health expenditure and decrease the individual financial burden of lung cancer.

First-line atezolizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer: a cost-effectiveness analysis from China.

Objective: To assess the cost-effectiveness of atezolizumab in combination with carboplatin plus nab-paclitaxel-based chemotherapy versus chemotherapy alone for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC) from the Chinese healthcare system perspective.Methods: A Markov model was developed based on the IMpower130 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included life-years (LYs), quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty.Results: When compared to chemotherapy alone, atezolizumab plus chemotherapy provides an additional 0.34 LY and 0.19 QALY, and has an ICER of $180,560.15 per additional LY gained and that of $325,328.71 per QALY gained. Sensitivity analysis revealed that the results were most sensitive to changes in atezolizumab cost. Probabilistic sensitivity analysis showed that there was a 0% probability that atezolizumab plus chemotherapy was cost-effective at willingness-to-pay values of $30,828 per QALY. If the WTP threshold increased to $325,000 per QALY, atezolizumab plus chemotherapy has a 50% chance to be cost-effective.Conclusions: From the Chinese healthcare system perspective, atezolizumab combination is not cost-effective for first-line therapy of advanced non-squamous NSCLC.

EGFR mutation-guided use of afatinib, erlotinib and gefitinib for advanced non-small-cell lung cancer in Hong Kong - A cost-effectiveness analysis.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) therapy targets at epidermal growth factor receptor (EGFR) gene mutations in non-small-cell lung cancer (NSCLC). We aimed to compare the EGFR mutation-guided target therapy versus empirical chemotherapy for first-line treatment of advanced NSCLC in the public healthcare setting of Hong Kong. METHODS: A Markov model was designed to simulate outcomes of a hypothetical cohort of advanced (stage IIIB/IV) NSCLC adult patients with un-tested EGFR-sensitizing mutation status. Four treatment strategies were evaluated: Empirical first-line chemotherapy with cisplatin-pemetrexed (empirical chemotherapy group), and EGFR mutation-guided use of a TKI (afatinib, erlotinib, and gefitinib). Model outcome measures were direct medical cost, progression-free survival, overall survival, and quality-adjusted life-years (QALYs). Incremental cost per QALY gained (ICER) was estimated. Sensitivity analyses were performed to examine robustness of model results. RESULTS: Empirical chemotherapy and EGFR mutation-guided gefitinib gained lower QALYs at higher costs than the erlotinib group. Comparing with EGFR mutation-guided erlotinib, the afatinib strategy gained additional QALYs with ICER (540,633 USD/QALY). In 10,000 Monte Carlo simulations for probabilistic sensitivity analysis, EGFR mutation-guided afatinib, erlotinib, gefitinib and empirical chemotherapy were preferred strategy in 0%, 98%, 0% and 2% of time at willingness-to-pay (WTP) 47,812 USD/QALY (1x gross domestic product (GDP) per capita), and in 30%, 68%, 2% and 0% of time at WTP 143,436 USD/QALY (3x GDP per capita), respectively. CONCLUSIONS: EGFR mutation-guided erlotinib appears to be the cost-effective strategy from the perspective of Hong Kong public healthcare provider over a broad range of WTP.