Cost-effectiveness and resource allocation (CERA) 18 years of evolution: maturity of adulthood and promise beyond tomorrow.

Since its inception in 2003, Cost Effectiveness and Resource Allocation journal has come a long way over the past 18 years. Possibly much longer than many of its contemporaries in the blossoming science of health economics might have anticipated. Today, entering 2020 it celebrates the Age of Maturity. We believe that in the third decade of XXI century the interdisciplinary science of health economics, will rejuvenate and come back to us younger than ever from its early historical roots almost a century ago. The spreading of economic globalization in several distinctive ways, either led by multinational business corporations or newly emerged Asian leadership, or both, is likely to make challenges for contemporary health systems far more serious. The fourth industrial revolution (cyber physical systems and artificial intelligence technology) and accelerated innovation in the field of E-Health and digital health, will probably change the workflow in medical and health care, and inevitably transform the labour market in the upcoming decades. So, let us be up to the task. Let us provide academic centres, industry-sponsored pharmaceutical and medical device innovation hubs, and governing authorities alike, with a powerful forum for debate on cost-effective resource allocation in the years to come.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III Trial.

BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. METHODS: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. RESULTS: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]. CONCLUSIONS: TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial.

BACKGROUND: Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. METHODS: This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. RESULTS: Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15-35 %) and arm B (24 % [16/68]; 95 % CI 13-34 %; P = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46-0.69) and 50 % (37/74; 95 % CI 0.39-0.61) in arms A and B, respectively (P = 0.45). Median PFS was 10.3 months (95 % CI 8.7-11.3) in arm A and 8.5 months (95 % CI 6.5-11.9) in arm B (P = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. CONCLUSION: This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3-5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine.

Cancer-related therapies at the end of life in hospitalized cancer patients from four Swiss cantons: SAKK 89/09.

The use of cancer-related therapies in cancer patients hospitalized at the end of life has increased in many countries over time. Given the scarcity of published Swiss data, the objective of this study was to evaluate the influence of hospital type and other factors on the delivery of health care during the last month before death. Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating Swiss cantons) who deceased between 2006 and 2008. Primary endpoints were delivery of cancer-related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of hospital type, patient and geographic characteristics. Of 3,809 identified cancer patients in the claims database, 2,086 patients dying from cancer were hospitalized during the last 30 days before death, generating 2,262 inpatient episodes. Anticancer drug therapy was given in 22.2% and radiotherapy in 11.7% of episodes. Besides age and cancer type, the canton of residence and hospital type showed independent, statistically significant associations with intensity of care, which was highest in university hospitals. These results should initiate a discussion among oncologists in Switzerland and may question the compliance with standard of care guidelines for terminal cancer patients.

Delivery of health care at the end of life in cancer patients of four swiss cantons: a retrospective database study (SAKK 89/09).

BACKGROUND: The use of cancer related therapy in cancer patients at the end-of-life has increased over time in many countries. Given a lack of published Swiss data, the objective of this study was to describe delivery of health care during the last month before death of cancer patients. METHODS: Claims data were used to assess health care utilization of cancer patients (identified by cancer registry data of four participating cantons), deceased between 2006-2008. Primary endpoints were hospitalization rate and delivery of cancer related therapies during the last 30 days before death. Multivariate logistic regression assessed the explanatory value of patient and geographic characteristics. RESULTS: 3809 identified cancer patients were included. Hospitalization rate (mean 68.5%, 95% CI 67.0-69.9) and percentage of patients receiving anti-cancer drug therapies (ACDT, mean 14.5%, 95% CI 13.4-15.6) and radiotherapy (mean 7.7%, 95% CI 6.7-8.4) decreased with age. Canton of residence and insurance type status most significantly influenced the odds for hospitalization or receiving ACDT. CONCLUSIONS: The intensity of cancer specific care showed substantial variation by age, cancer type, place of residence and insurance type status. This may be partially driven by cultural differences within Switzerland and the cantonal organization of the Swiss health care system.

Costs differences among monoclonal antibodies-based first-line oncology cancer protocols for breast cancer, colorectal carcinoma and non-Hodgkin's lymphoma.

PURPOSE: To assess and compare the costs of first-line monoclonal antibodies (mAbs) treatment protocols in breast cancer, non-Hodgkin lymphoma and colorectal carcinoma in South-Eastern Europe. METHODS: A retrospective, bottom-up case series study design was implemented with one-year time horizon and payer's perspective. The study sample size was 265 patients (breast cancer, N=137; colorectal cancer, N=44; and non-Hodgkin lymphoma, N=84), while treatment protocols included adjuvant mAbs: trastuzumab (N=137), bevacizumab (N=28), rituximab (N=16) and cetuximab (N=84). ICD-10 related resources use included history of medical services utilization, chronology (time out of service provision) and unit consumption of examinations, drugs prescribed, imaging, radiotherapy and surgical procedures provided etc., direct medical and lost productivity costs (€) across treatment groups during 2010-2013. RESULTS: The average length of observation was 125+97 days per patient. Total mean direct and indirect costs of care were: trastuzumab for breast cancer group € 17,740 per patient; bevacizumab for colorectal carcinoma group €8,775 per patient; cetuximab for colorectal carcinoma group € 27,181 per patient; and rituximab for non-Hodgkin lymphoma group €19,431 per patient. An average mAbs-treated patient incurred €17,897 costs of medical care. The total combined budget of these 330 patients was €4,742,775. CONCLUSIONS: The use of mAbs strongly correlated with high costs in first-line cancer medical care and dominated other cost domains. Cetuximab-based treatment protocols in colorectal carcinoma patients was substantially more expensive compared to trastuzumab (C50), bevacizumab (C20), and rituximab (C80) alternatives. Extremely high costs of mAbs are the key-issue for Eastern European policy makers by crossing the upper limits of affordability in middle-income economies.

Clinical characteristics and therapeutic behavior of breast cancer patients using mistletoe therapy consulting a clinic offering integrative oncology: a registry data analysis.

MOTIVATION: Cancer patients often use complementary and/or alternative medicine, such as mistletoe therapy, alongside conventional cancer therapies. In Switzerland, so far not much is known about treatment patterns of breast cancer patients using integrative oncology. Solid knowledge on complementary care utilization may help to enhance integrative oncology care in Switzerland. METHODS: In this exploratory, descriptive database study, we investigated the treatment pathways of a cohort of breast cancer patients who received mistletoe therapy and were documented in the cancer registry of an anthroposophic Swiss hospital offering integrative oncology treatments. RESULTS: Patients treated with mistletoe in this cohort are in median 10 years younger than Swiss breast cancer patients as a whole. Only 5.8% of these patients were treated with mistletoe alone, while 60.5% of them supplemented chemotherapy and/or hormone therapy and/or surgery and/or radiation with mistletoe therapy. Nearly 80% of patients started conventional therapy followed by additional mistletoe therapy or started mono mistletoe therapy after completion of conventional therapies. The median time from initial diagnosis to hospital admission (inpatient and/or outpatient) was less than one year. Almost ¾ of the patients were treated in an outpatient setting only. CONCLUSION: From our data, it appears that younger breast cancer patients are more likely to use mistletoe therapy simultaneously with or following their conventional medical therapies. The extent to which these patients discuss their mistletoe therapy and eventually other complementary and/or alternative therapies with their primary oncologists is not clear from the data. We therefore recommend that (Swiss) oncologists should openly discuss the desire for integrative oncology therapies, especially with their younger breast cancer patients, in order to find the best holistic care pattern for these patients.

Cost-effectiveness of maintenance pemetrexed in patients with advanced nonsquamous-cell lung cancer from the perspective of the Swiss health care system.

OBJECTIVES: A recent randomized study showed switch maintenance with pemetrexed after nonpemetrexed-containing first-line chemotherapy in patients with advanced nonsmall-cell lung cancer to prolong overall survival by 2.8 months. We examined the cost-effectiveness of pemetrexed in this indication, from the perspective of the Swiss health care system, and assessed the influence of the costs of best supportive care (BSC) on overall cost-effectiveness. METHODS: A Markov model was constructed based on the pemetrexed maintenance study, and the incremental cost-effectiveness ratio (ICER) of adding pemetrexed until disease progression was calculated as cost per quality-adjusted life-year gained. Uncertainties concerning the costs of BSC on the ICER were addressed. RESULTS: The base case ICER for maintenance therapy with pemetrexed plus BSC compared to BSC alone was €106,202 per quality-adjusted life-year gained. Varying the costs for BSC had a marked effect. Assuming a reduction of the costs for BSC by 25% in the pemetrexed arm resulted in an ICER of €47,531 per quality-adjusted life-year, which is below predefined criteria for cost effectiveness in Switzerland. CONCLUSIONS: Switch maintenance with pemetrexed in patients with advanced nonsquamous-cell lung cancer after standard first-line chemotherapy is not cost-effective. Uncertainties on the resource use and costs for BSC have a large influence on the cost-effectiveness calculation and should be reported in more detail.

Handling Uncertainty in Cost-Effectiveness Analysis: Budget Impact and Risk Aversion.

Methods to handle uncertainty in economic evaluation have gained much attention in the literature, and the cost-effectiveness acceptability curve (CEAC) is the most widely used method to summarise and present uncertainty associated with program costs and effects in cost-effectiveness analysis. Some researchers have emphasised the limitations of the CEAC for informing decision and policy makers, as the CEAC is insensitive to radial shifts of the joint distribution of incremental costs and effects in the North-East and South-West quadrants of the cost-effective plane (CEP). Furthermore, it has been pointed out that the CEAC does not incorporate risk-aversion in valuing uncertain costs and effects. In the present article, we show that the cost-effectiveness affordability curve (CEAFC) captures both dimensions of the joint distribution of incremental costs and effects on the CEP and is, therefore, sensitive to radial shifts of the joint distribution on the CEP. Furthermore, the CEAFC also informs about the budget impact of a new intervention, as it can be used to estimate the joint probability that an intervention is both affordable and cost-effective. Moreover, we show that the cost-effectiveness risk-aversion curve (CERAC) allows the analyst to incorporate different levels of risk-aversion into the analysis and can, therefore, be used to inform decision-makers who are risk-averse. We use data from a published cost-effectiveness model of palbociclib in addition to letrozole versus letrozole alone for the treatment of oestrogen-receptor positive, HER-2 negative, advanced breast cancer to demonstrate the differences between CEAC, CEAFC and CERAC, and show how these can jointly be used to inform decision and policy makers.

Impact of treatment decision algorithms on treatment costs in recurrent glioblastoma: a health economic study.

AIMS: Recurrent glioblastoma (GBM) is a disease with poor prognosis. Although several therapeutic approaches such as chemotherapy, irradiation or surgery have been investigated, there is no established standard therapy. A recent survey among Swiss neuro-oncology centres has shown considerable controversy in the treatment recommendations for any specific scenario of recurrent GBM. In view of the cost differences of the available treatment alternatives, the aim of our study was assess the financial impact of different institutional therapeutic strategies for recurrent GBM in Switzerland. METHODS: We created a decision analytic model for each of the eight centres participating in the initial study with a centre-specific treatment algorithm to evaluate the average treatment cost per patient. The probability of decision criteria was varied by univariate and probabilistic sensitivity analysis over a wide range to account for the high level of uncertainty. Treatment costs were calculated from the perspective of the Swiss healthcare payer. RESULTS: Mean treatment costs per patient calculated on the basis of the institutional treatment algorithms ranged from CHF 13,748 to CHF 22,072 depending on the probability of individual decision criteria. The most influential decision factors for the mean treatment costs were the probability of fit patients and the proportion of patients with resectable tumour recurrences. There was a significant correlation between the complexity of treatment algorithms in a centre and the resulting mean treatment costs. CONCLUSIONS: Institutional treatment algorithms can be used to estimate the average treatment costs per patient, which are, however, highly sensitive to probability changes of individual decision criteria. Our study demonstrates a high variability in treatment costs for recurrent GBM among eight Swiss neuro-oncology centres based on individual institutional treatment algorithms.

A cost-effectiveness analysis of consolidative local therapy in oligometastatic non-squamous non-small cell lung cancer (NSCLC).

BACKGROUND: Novel systemic therapies have improved the prognosis of metastatic non-small cell lung cancer (NSCLC), but costs of some of these drugs are a matter of ongoing debate. More recently, local therapies (LT) such as radiotherapy and surgery have been suggested as additional treatment in oligometastatic NSCLC demonstrating an improved progression-free survival (PFS) in a phase II trial compared to maintenance chemotherapy (MC) alone. The aim of this analysis was to assess the cost-effectiveness of local therapies in oligometastatic NSCLC. METHODS: We constructed a Markov model comparing the cost-effectiveness of LT versus MC for oligometastatic NSCLC from the Swiss healthcare payer's perspective. Treatment specifications and PFS were based on the phase II trial (NCT01725165). Overall survival (OS) was inferred from a recent phase III trial. Utilities were taken from published data. Primary outcome was the incremental cost-effectiveness-ratio (ICER, costs in Swiss Francs (CHF) per quality-adjusted life-year (QALY) gained). RESULTS: PFS in the model was 3.8 months for MC and 11.4 months for LT (compared to 3.9 months and 11.9 months in the trial). OS in the model was 15.5 months in both arms. LT was cost-effective with a gain of 0.24 QALYs at an additional cost of CHF 9641, resulting in an ICER of CHF 40,972/QALY gained. Probabilistic sensitivity analyses demonstrated that LT was dominant or cost-effective at a willingness-to-pay threshold of CHF 100,000 per QALY in 61.7% of the simulations. CONCLUSIONS: LT may be cost-effective for selected patients with oligometastatic NSCLC responding to first-line systemic therapy.

Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Maintenance Therapy for Patients With Advanced Nonsquamous Non-Small-cell Lung Cancer: Update From the Swiss Group for Clinical Cancer Research (SAKK) 19/09 Trial.

BACKGROUND: Pemetrexed and bevacizumab as single agents have been approved for maintenance therapy after platinum-based induction in patients with advanced nonsquamous non-small-cell lung cancer. It is currently unknown whether bevacizumab plus pemetrexed is superior to pemetrexed alone. PATIENTS AND METHODS: We conducted a nonrandomized phase II trial with 2 sequential cohorts. In the first cohort, 77 patients were treated with 4 cycles of cisplatin, bevacizumab, and pemetrexed every 3 weeks, followed by bevacizumab plus pemetrexed maintenance until progression. In the second cohort, we treated 52 patients without bevacizumab, using maintenance with pemetrexed alone. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), adverse events, and the treatment costs of the 2 cohorts were compared. RESULTS: The median PFS from the time of registration was 6.9 months in cohort 1 and 5.6 months in cohort 2. The ORR was 62.3% in cohort 1% and 44.2% in cohort 2. The PFS (hazard ratio, 0.7; 95% confidence interval [CI], 0.5-1.0; P = .041) and ORR (odds ratio, 2.1; 95% CI, 1.0-4.3; P = .049) were better in cohort 1 than in cohort 2. No OS difference was found (hazard ratio, 1.0; 95% CI, 0.7-1.6; P = .890) after a median follow-up period of 47 months for cohort 1 and 27 months for cohort 2. The rate of grade ≥ 3 adverse events was greater in cohort 1. The treatment costs per patient were on average 1.4 times greater for cohort 1. CONCLUSION: The addition of bevacizumab increased the ORR and PFS, but not OS, in our nonrandomized trial. Furthermore, the addition of bevacizumab was associated with greater toxicity and higher costs.

Seasonal variation in orthopedic health services utilization in Switzerland: the impact of winter sport tourism.

BACKGROUND: Climate- or holiday-related seasonality in hospital admission rates is well known for many diseases. However, little research has addressed the impact of tourism on seasonality in admission rates. We therefore investigated the influence of tourism on emergency admission rates in Switzerland, where winter and summer leisure sport activities in large mountain regions can generate orthopedic injuries. METHODS: Using small area analysis, orthopedic hospital service areas (HSAo) were evaluated for seasonality in emergency admission rates. Winter sport areas were defined using guest bed accommodation rate patterns of guest houses and hotels located above 1000 meters altitude that show clear winter and summer peak seasons. Emergency admissions (years 2000-2002, n = 135'460) of local and nonlocal HSAo residents were evaluated. HSAo were grouped according to their area type (regular or winter sport area) and monthly analyses of admission rates were performed. RESULTS: Of HSAo within the defined winter sport areas 70.8% show a seasonal, summer-winter peak hospital admission rate pattern and only 1 HSAo outside the defined winter sport areas shows such a pattern. Seasonal hospital admission rates in HSAo in winter sport areas can be up to 4 times higher in winter than the intermediate seasons, and they are almost entirely due to admissions of nonlocal residents. These nonlocal residents are in general -and especially in winter- younger than local residents, and nonlocal residents have a shorter length of stay in winter sport than in regular areas. The overall geographic distribution of nonlocal residents admitted for emergencies shows highest rates during the winter as well as the summer in the winter sport areas. CONCLUSION: Small area analysis using orthopedic hospital service areas is a reliable method for the evaluation of seasonality in hospital admission rates. In Switzerland, HSAo defined as winter sport areas show a clear seasonal fluctuation in admission rates of only nonlocal residents, whereas HSAo defined as regular, non-winter sport areas do not show such seasonality. We conclude that leisure sport, and especially ski/snowboard tourism demands great flexibility in hospital beds, staff and resource planning in these areas.

Analysis of patient flows for orthopedic procedures using small area analysis in Switzerland.

BACKGROUND: In general cantons regulate and control the Swiss health service system; patient flows within and between cantons are thereby partially disregarded. This paper develops an alternative spatial model, based upon the construction of orthopedic hospital service areas (HSAOs), and introduces indices for the analysis of patient streams in order to identify areas, irrespective of canton, with diverse characteristics, importance, needs, or demands. METHODS: HSAOs were constructed using orthopedic discharge data. Patient streams between the HSAOs were analysed by calculating three indices: the localization index (% local residents discharged locally), the netindex (the ratio of discharges of nonlocal incoming residents to outgoing local residents), and the market share index (% of local resident discharges of all discharges in local hospitals). RESULTS: The 85 orthopedic HSAOs show a median localization index of 60.8%, a market share index of 75.1%, and 30% of HSAOs have a positive netindex. Insurance class of bed, admission type, and patient age are partially but significantly associated with those indicators. A trend to more centrally provided health services can be observed not only in large urban HSAOs such as Geneva, Bern, Basel, and Zurich, but also in HSAOs in mountain sport areas such as Sion, Davos, or St.Moritz. Furthermore, elderly and emergency patients are more frequently treated locally than younger people or those having elective procedures. CONCLUSION: The division of Switzerland into HSAOs provides an alternative spatial model for analysing and describing patient streams for health service utilization. Because this small area model allows more in-depth analysis of patient streams both within and between cantons, it may improve support and planning of resource allocation of in-patient care in the Swiss healthcare system.

Is the EQ-5D suitable for use in oncology? An overview of the literature and recent developments.

The European Quality of Life-5 Dimensions (EQ-5D) questionnaire is widely used in oncology to generate quality of life weights (utilities). The typical purpose is to inform health economic evaluation studies. The EQ-5D is generally suitable for this purpose; it has shown a reasonable degree of reliability, content validity, construct validity and responsiveness in the majority of the available studies. In situations of doubt, combination with other quality-of-life instruments may be an option. The authors expect that the five-level version of the EQ-5D will gradually replace the three-level version, due to reduced ceiling effects and more appropriate responsiveness. Further research should address the benefits achievable through additional dimensions or patient-based valuation, and the validity of EQ-5D versions for proxy respondents.

Bevacizumab Continuation Versus Treatment Holidays After First-Line Chemotherapy With Bevacizumab in Patients With Metastatic Colorectal Cancer: A Health Economic Analysis of a Randomized Phase 3 Trial (SAKK 41/06).

BACKGROUND: Bevacizumab (BEV)-containing therapies are costly. We performed a health economic analysis of a randomized phase 3 study (SAKK 41/06) that compared BEV continuation as a single agent (BEV) with treatment holidays (no BEV) after completing 4 to 6 cycles of first-line chemotherapy plus BEV in metastatic colorectal cancer patients. PATIENTS AND METHODS: Costs for first-line chemotherapy with BEV, BEV continuation therapy, hospitalizations (length of stay), control visits, diagnostic tests, and second-line and later rounds of chemotherapy were collected. Mean costs per patient per treatment arm and an incremental cost-effectiveness ratio were calculated. Probabilistic sensitivity analysis was performed to account for uncertainty in the input parameters. RESULTS: The total incurred mean costs per patient were 126,631 Swiss francs (CHF) [95% confidence interval (CI), 116,521-136,740] for BEV versus CHF100,146 (95% CI, 92,811-107,481) for no BEV. The incremental cost effectiveness ratio was CHF108,991 per life-year gained (LYG; 95% CI from probabilistic sensitivity analysis, 62,890-248,515). Compared to a willingness-to-pay threshold of CHF100,000/LYG, there was 42% probability that BEV continuation was cost effective, which decreased to 20% at a threshold of CHF75,000/LYG. Economic equality was reached in only 0.07% of cases. CONCLUSION: The clinical conclusion that BEV continuation as a single agent after completion of first-line chemotherapy is of low therapeutic value is supported by this health economic analysis. Costs increase without significant clinical benefit in this setting.

A Cost-Effectiveness Analysis of Nivolumab versus Docetaxel for Advanced Nonsquamous NSCLC Including PD-L1 Testing.

INTRODUCTION: Nivolumab (NIV) was recently approved in several countries for patients with pretreated advanced NSCLC. NIV is not cost-effective compared with docetaxel (DOC) for the treatment of squamous NSCLC. However, its cost-effectiveness for nonsquamous NSCLC and the consequences of programmed death ligand 1 (PD-L1) testing are unknown. METHODS: This literature-based health economic study used CheckMate-057 trial data to model the incremental cost-effectiveness ratio (ICER) of NIV versus DOC in the Swiss health care setting. The effect of PD-L1 positivity for patient selection was assessed. RESULTS: In the base case model, NIV (mean cost CHF66,208; mean effect 0.69 quality-adjusted life-years [QALYs]) compared with DOC (mean cost CHF37,618; mean effect 0.53 QALYs) resulted in an ICER of CHF177,478/QALY gained. Treating only patients with PD-L1-positive tumors (threshold ≥10%) with NIV compared with treating all patients with DOC produced a base case ICER of CHF124,891/QALY gained. Reduced drug price, dose, or treatment duration decreased the ICER partly below a willingness-to-pay threshold of CHF100,000/QALY. Health state utilities strongly influenced cost-effectiveness. CONCLUSIONS: Compared with DOC, NIV is not cost-effective for the treatment of nonsquamous NSCLC at current prices in the Swiss health care setting. Price reduction or PD-L1 testing and selection of patients for NIV on the basis of test positivity improves cost-effectiveness compared with DOC.

End-of-life costs of medical care for advanced stage cancer patients.

BACKGROUND/AIM: Cancer, one of the leading causes of mortality in the world, imposes a substantial economic burden on each society, including Serbia. The aim of this study was to evaluate the major cancer cost drivers in Serbia. METHODS: A retrospective, in-depth, bottom-up analysis of two combined databases was performed in order to quantify relevant costs. End-of-life data were obtained from patients with cancer, who deceased within the first year of the established diagnose, including basic demographics, diagnosis, tumour histology, medical resource use and related costs, time and cause of death. All costs were allocated to one of the three categories of cancer health care services: primary care (included home care), hospital outpatient and hospital inpatient care. RESULTS: Exactly 114 patients were analyzed, out of whom a high percent (48.25%) had distant metastases at the moment of establishing the diagnosis. Malignant neoplasms of respiratory and intrathoracic organs were leading causes of morbidity. The average costs per patient were significantly different according to the diagnosis, with the highest (13,114.10 EUR) and the lowest (4.00 EUR) ones observed in the breast cancer and melanoma, respectively. The greatest impact on total costs was observed concerning pharmaceuticals, with 42% of share (monoclonal antibodies amounted to 34% of all medicines and 14% of total costs), followed by oncology medical care (21%), radiation therapy and interventional radiology (11%), surgery (90%), imaging diagnostics (9%) and laboratory costs (8%). CONCLUSION. Cancer treatment incurs high costs, especially for end-of-life pharmaceutical expenses, ensued from medical personnel tendency to improve such patients' quality of life in spite of nearing the end of life. Reimbursement policy on monoclonal antibodies, in particular at end-stage disease, should rely on cost-effectiveness evidence as well as documented clinical efficiency.

Using the EuroQol EQ-5D in Swiss cancer patients, which value set should be applied?

BACKGROUND: The European Quality of Life-5 Dimensions (EQ-5D) instrument combines questionnaire responses into a single utility estimate using country-specific value sets. Countries without a national value set are advised to select one based on geographic proximity. In the absence of a Swiss value set, we used foreign value sets to gain insights into their appropriateness for use with Swiss cancer patients. METHODS: EQ-5D health states and visual analogue scale (VAS) ratings were collected in one German and three Swiss oncology trials. Utilities were calculated based on the United Kingdom (UK), German (GE), French (FR) and European Union (EU) value sets. Resulting differences and Pearson partial correlation coefficients with corresponding VAS ratings were assessed. RESULTS: In total, 202 Swiss and 154 German patients undergoing cancer treatment completed at least two EQ-5D forms. The mean difference between GE-based and FR-, UK- or EU-based utilities was significantly larger than the differences between the latter. The absolute mean difference between utilities and VAS ratings was highest for GE-based utilities, for Swiss (0.170, 95 % confidence interval [CI] 0.146-0.194) and German patients (0.174, 95 % CI 0.145-0.202). The correlation between GE-based utilities and VAS ratings was the lowest (r = 0.36, 95 % CI 0.33-0.40); the highest was between FR-based utilities and VAS ratings (r = 0.43, 95 % CI 0.39-0.46). CONCLUSION: For Switzerland, utility calculations based on the German or French value set would be an obvious choice. Our results suggest that the German value set may not be the most appropriate for use with Swiss cancer patients. The French and EU value sets may be relevant alternatives and improve international comparability.

Bevacizumab in combination with paclitaxel for HER-2 negative metastatic breast cancer: an economic evaluation.

The addition of bevacizumab to weekly paclitaxel as primary chemotherapy for HER-2 negative metastatic breast cancer (MBC) prolongs progression-free survival without a substantial increase of toxicity. A Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Information on response rates and major adverse effects was derived, and transition probabilities were estimated, based on the results of the E2100 clinical trial. Direct costs were assessed from the perspective of the Swiss health system. The addition of bevacizumab to weekly paclitaxel is estimated to cost an additional 40,369euro and to yield a gain of 0.22 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of 189,427euro/QALY gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of 60,000euro was never reached. The addition of bevacizumab to paclitaxel in MBC patients is expensive given the clinical benefit in terms of QALYs gained.