Reply to comment by Arber C, et al. on: Real-world expenditures and survival time after CAR-T treatment for large B-cell lymphoma in Switzerland.

No abstract available.

Cost-Effectiveness Analysis of Etranacogene Dezaparvovec Versus Extended Half-Life Prophylaxis for Moderate-to-Severe Haemophilia B in Germany.

BACKGROUND AND OBJECTIVE: Haemophilia B is a rare genetic disease that is caused by a deficiency of coagulation factor IX (FIX) in the blood and leads to internal and external bleeding. Under the current standard of care, haemophilia is treated either prophylactically or on-demand via intravenous infusions of FIX. These treatment strategies impose a high burden on patients and health care systems as haemophilia B requires lifelong treatment, and FIX is costly. Etranacogene dezaparvovec (ED) is a gene therapy for haemophilia B that has been recently approved by the United States Food and Drug Administration and has received a recommendation for conditional marketing authorization by the European Medicines Agency. We aimed to examine the cost-effectiveness of ED versus extended half-life FIX (EHL-FIX) prophylaxis for moderate-to-severe haemophilia B from a German health care payer perspective. METHODS: A microsimulation model was implemented in R. The model used data from the ED phase 3 clinical trial publication and further secondary data sources to simulate and compare patients receiving ED or EHL-FIX prophylaxis over a lifetime horizon, with the potential for ED patients to switch treatment to EHL-FIX prophylaxis when the effectiveness of ED waned. Primary outcomes of this analysis included discounted total costs, discounted quality-adjusted life years (QALYs), incremental cost-effectiveness, and the incremental net monetary benefit. The annual discount rate for costs and effects was 3%. Uncertainty was examined via probabilistic analysis and additional univariate sensitivity analyses. RESULTS: Probabilistic analysis indicated that patients treated with ED instead of EHL-FIX prophylaxis gained 0.50 QALYs and experienced cost savings of EUR 1,179,829 at a price of EUR 1,500,000 per ED treatment. ED was the dominant treatment strategy. At a willingness to pay of EUR 50,000/QALY, the incremental net monetary benefit amounted to EUR 1,204,840. DISCUSSION: Depending on the price, ED can save costs and improve health outcomes of haemophilia patients compared with EHL-FIX prophylaxis, making it a potentially cost-effective alternative. These results are uncertain due to a lack of evidence regarding the long-term effectiveness of ED.

Separating the wheat from the chaff: How to measure hospital quality in routine data?

OBJECTIVE: To measure hospital quality based on routine data available in many health care systems including the United States, Germany, the United Kingdom, Scandinavia, and Switzerland. DATA SOURCES AND STUDY SETTING: We use the Swiss Medical Statistics of Hospitals, an administrative hospital dataset of all inpatient stays in acute care hospitals in Switzerland for the years 2017-2019. STUDY DESIGN: We study hospital quality based on quality indicators used by leading agencies in five countries (the United States, the United Kingdom, Germany, Austria, and Switzerland) for two high-volume elective procedures: inguinal hernia repair and hip replacement surgery. We assess how least absolute shrinkage and selection operator (LASSO), a supervised machine learning technique for variable selection, and Mundlak corrections that account for unobserved heterogeneity between hospitals can be used to improve risk adjustment and correct for imbalances in patient risks across hospitals. DATA COLLECTION/EXTRACTION METHODS: The Swiss Federal Statistical Office collects annual data on all acute care inpatient stays including basic socio-demographic patient attributes and case-level diagnosis and procedure codes. PRINCIPAL FINDINGS: We find that LASSO-selected and Mundlak-corrected hospital random effects logit models outperform common practice logistic regression models used for risk adjustment. Besides the more favorable statistical properties, they have superior in- and out-of-sample explanatory power. Moreover, we find that Mundlak-corrected logits and the more complex LASSO-selected models identify the same hospitals as high or low-quality offering public health authorities a valuable alternative to standard logistic regression models. Our analysis shows that hospitals vary considerably in the quality they provide to patients. CONCLUSION: We find that routine hospital data can be used to measure clinically relevant quality indicators that help patients make informed hospital choices.

Burden of seasonal influenza in the Swiss adult population during the 2016/2017-2018/2019 influenza seasons.

BACKGROUND: Evidence on the burden of seasonal influenza in Switzerland is scarce, yet it is critical for the design of effective prevention and control measures. The objective of this study was to assess influenza-related resource utilization, health care expenditures and quality-adjusted life-years (QALYs) lost in Switzerland across the 2016/2017-2018/2019 influenza seasons. METHODS: We retrospectively analyzed multiple real-world data sources to calculate epidemiological and health outcomes, QALYs lost, and direct medical costs due to influenza in the Swiss adult population. Subgroups included residents 18-49, 50-64, and 65+ years of age. The observation period was Week 26, 2016, to Week 25, 2019. RESULTS: Across the three seasons, we estimated seasonal averages of 203,090 (se ± 26,717) general practitioner (GP) visits for influenza-like illness (ILI) 4944 (se ± 785) influenza-attributable hospitalizations and 1355 (se ± 169) excess deaths attributable to influenza. We estimated a total loss of 8429 (2016/2017), 11,179 (2017/2018), and 7701 (2018/2019) QALYs due to influenza. On average, 88% of the loss in QALYs was attributed to premature deaths due to influenza. The total direct medical costs amounted to 44.4 (2016/2017), 77.3 (2017/2018), and 64.5 (2018/2019) million euros. On average, 79.6% of the total costs arose due to hospitalizations. CONCLUSIONS: In Switzerland, the burden of influenza on patients and payers is significant and particularly high in the elderly population. Policy interventions to increase vaccination rates and the uptake of more effective vaccines among the elderly are needed to reduce the burden of influenza.

Real-world expenditures and survival time after CAR-T treatment for large B-cell lymphoma in Switzerland: a retrospective study using insurance claims data.

AIM OF THE STUDY: Newly approved therapies with high and uncertain budget impact pose challenges to public health care systems worldwide. One recent example is chimeric antigen receptor T cell (CAR-T) therapies for adults with large B-cell lymphoma (LBCL). This study's primary objective is to examine the expenditures of Swiss public payers before, during, and after CAR-T cell therapy in patients with LBCL aged ≥30 years. Its secondary objective is to analyse 24-month survival rates. METHODS: This retrospective observational data analysis used the administrative databases of the Swiss health insurers Concordia, CSS, Groupe Mutuel, Helsana, ÖKK, Sanitas, SWICA, Sympany, and Visana. These health insurers or groups provide mandatory health insurance to approximately 78% of Swiss residents in 2021. Using the relevant procedure codes, we identified CAR-T therapies administered between October 2018 (first approval) and June 2021 (treatment identification cut-off). Patients aged <30 years were excluded because they might be treated for pediatric acute lymphoblastic leukaemia. Expenditures were categorised as pre-infusion, peri-infusion (excluding CAR-T therapy acquisition costs), and post-infusion based on the time of service provision. Overall survival rates were estimated using the Kaplan-Meier method. RESULTS: This study identified 81 patients aged ≥30 years, with a median follow-up period for censored observations of 27 months (interquartile range: 21-31 months). The median age group was 70-74, and 60% of patients were male. Mean healthcare expenditures per patient per month amounted to CHF 8,115-22,564 pre-infusion, CHF 38,490 peri-infusion, and CHF 5,068-11,342 post-infusion. For the total peri- and post-infusion period (i.e. 1-month before infusion to 23 months after infusion), mean healthcare expenditures amounted to CHF 215,737. The 24-month overall survival rate was 48% (95% confidence interval: 38-61%). CONCLUSIONS: Healthcare expenditures after CAR-T cell infusion are relatively high compared to previous estimates of patients with LBCL in the last year of treatment. Further research is needed to understand the drivers behind these post-infusion expenditures. Especially, clinical data should be used to assess the time until disease progression. The analysis of 24-month overall survival is consistent with results from the pivotal trials. Our findings stress the importance of post-approval studies to monitor real-world expenditures and outcomes related to innovative therapies.

Cost-effectiveness of HLA-DQB1/HLA-B pharmacogenetic-guided treatment and blood monitoring in US patients taking clozapine.

Less than 1% of adult patients with schizophrenia taking clozapine develop agranulocytosis, and most of these cases occur within the first weeks of treatment. The human leukocyte antigen (HLA) region has been associated with genetic susceptibility to clozapine-induced agranulocytosis (single amino acid changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate the cost-effectiveness, from a healthcare provider's perspective, of an HLA genotype-guided approach in patients with treatment-resistant schizophrenia who were taking clozapine and to compare the results with the current absolute neutrophil count monitoring (ANCM) schemes used in the USA. A semi-Markovian model was developed to simulate the progress of a cohort of adult men and women who received clozapine as a third-line antipsychotic medication. We compared current practices using two genotype-guided strategies: (1) HLA genotyping followed by clozapine, with ANCM only for patients who tested positive for one or both alleles (genotype-guided blood sampling); (2) HLA genotyping followed by clozapine for low-risk patients and alternative antipsychotics for patients who tested positive (clozapine substitution scheme). Up to a decision threshold of $3.9 million per quality-adjusted life-year (90-fold the US gross domestic product per capita), the base-case results indicate that compared with current ANCM, genotype-guided blood sampling prior to clozapine initiation appeared cost-effective for targeted blood monitoring only in patients with HLA susceptibility alleles. Sensitivity analysis demonstrated that at a cost of genotype testing of up to USD700, HLA genotype-guided blood monitoring remained a cost-effective strategy compared with either current ANCM or clozapine substitution.

How much does the treatment of each major disease cost? A decomposition of Swiss National Health Accounts.

In most countries, surprisingly little is known on how national healthcare spending is distributed across diseases. Single-disease cost-of-illness studies cover only a few of the diseases affecting a population and in some cases lead to untenably large estimates. The objective of this study was to decompose healthcare spending in 2011, according to Swiss National Health Accounts, into 21 collectively exhaustive and mutually exclusive major disease categories. Diseases were classified following the Global Burden of Disease Study. We first assigned the expenditures directly mapping from National Health Accounts to the 21 diseases. The remaining expenditures were assigned based on diagnostic codes and clues contained in a variety of microdata sources. Expenditures were dominated by non-communicable diseases with a share of 79.4%. Cardiovascular diseases stood out with 15.6% of total spending, followed by musculoskeletal disorders (13.4%), and mental and substance use disorders (10.6%). Neoplasms (6.0% of the total) ranked only sixth, although they are the leading cause of premature death in Switzerland. These results may be useful for the design of health policies, as they illustrate how healthcare spending is influenced by the epidemiological transition and increasing life expectancy. They also provide a plausibility check for single cost-of-illness studies. Our study may serve as a starting point for further research on the drivers of the constant growth of healthcare spending.

The effects of organized screening programs on the demand for mammography in Switzerland.

The objective of this study is to estimate the causal effect of organized mammography screening programs on the proportion of women between 50 and 69 years of age who have ever used mammography. We exploit the gradual implementation of organized screening programs in nine Swiss cantons using a difference-in-difference approach. An analysis of four waves of the Swiss Health Survey shows that 3.5-5.4% points of the 87.9% utilization rate in cantons with screening programs in 2012 can be attributed to these organized programs. This effect indicates that organized programs can motivate women who have never done mammography to initiate screening.

Health utility indexes in patients with acute coronary syndromes.

BACKGROUND: Acute coronary syndromes (ACS) have been associated with lower health utilities (HUs) compared with the general population. Given the prognostic improvements after ACS with the implementation of coronary angiography (eg, percutaneous coronary intervention (PCI)), contemporary HU values derived from patient-reported outcomes are needed. METHODS: We analysed data of 1882 patients with ACS 1 year after coronary angiography in a Swiss prospective cohort. We used the EuroQol five-dimensional questionnaire (EQ-5D) and visual analogue scale (VAS) to derive HU indexes. We estimated the effects of clinical factors on HU using a linear regression model and compared the observed HU with the average values of individuals of the same sex and age in the general population. RESULTS: Mean EQ-5D HU 1-year after coronary angiography for ACS was 0.82 (±0.16) and mean VAS was 0.77 (±0.18); 40.9% of participants exhibited the highest utility values. Compared with population controls, the mean EQ-5D HU was similar (expected mean 0.82, p=0.58) in patients with ACS, but the mean VAS was slightly lower (expected mean 0.79, p<0.001). Patients with ACS who are younger than 60 years had lower HU than the general population (<0.001). In patients with ACS, significant differences were found according to the gender, education and employment status, diabetes, obesity, heart failure, recurrent ischaemic or incident bleeding event and participation in cardiac rehabilitation (p<0.01). CONCLUSIONS: At 1 year, patients with ACS with coronary angiography had HU indexes similar to a control population. Subgroup analyses based on patients' characteristics and further disease-specific instruments could provide better sensitivity for detecting smaller variations in health-related quality of life.

Cost-effectiveness of functional cardiac imaging in the diagnostic work-up of coronary heart disease.

AIMS: The aim of this study was to assess the cost-effectiveness of eight common diagnostic work-up strategies for coronary heart disease (CHD) in patients with stable angina symptoms in Switzerland. METHODS AND RESULTS: A decision analytical model was used to perform a cost-effectiveness comparison of eight common multitest strategies to diagnose CHD using combinations of four diagnostic techniques: exercise treadmill test (ETT), single-photon emission computed tomography (SPECT), cardiac magnetic resonance imaging (CMR), and coronary angiography (CA). We used a Markov state transition model to extrapolate the results over a life-time horizon, from a third-party payer perspective. We used a CHD prevalence rate of 39% in patients and a base-case scenario with 60-year-old male patients with intermediate symptom severity Canadian Cardiovascular Society grading of angina pectoris 2 and at least one cardiovascular (CV) risk factor but without a history of myocardial infarction and without need for revascularization. Among the eight work-up strategies, one strategy was dominant, i.e. least costly and most effective: ETT followed by CMR if the ETT result was inconclusive and then CA if the CMR result was positive or inconclusive. The CMR features a favourable balance between false-negative diagnoses, associated with an elevated risk of CV events, and false-positive diagnoses, leading to unnecessary CA and related mortality. Key parameters guiding the diagnostic strategy are the prevalence of CHD in patients with angina symptoms and the diagnostic costs of CA and CMR. CONCLUSION: Cardiac magnetic resonance imaging appears to be a cost-effective work-up strategy compared with other regimens using SPECT or direct CA. Cardiac magnetic resonance imaging should be more widely recommended as a diagnostic procedure for patients with suspected angina symptoms.

Marginal revenue and length of stay in inpatient psychiatry.

This study examines the changes in marginal revenue during psychiatric inpatient stays in a large Swiss psychiatric hospital after the introduction of a mixed reimbursement system with tariff rates that vary over length of stay. A discrete time duration model with a difference-in-difference specification and time-varying coefficients is estimated to assess variations in policy effects over length of stay. Among patients whose costs are fully reimbursed by the mixed scheme, the model demonstrates a significant effect of marginal revenue on length of stay. No significant policy effects are found among patients for whom only health insurance rates are delivered as mixed tariffs and government contributions are made retrospectively. The results indicate that marginal revenue can affect length of stay in inpatient psychiatry facilities, but that the reduction in marginal revenue must be sufficiently large.

The Societal Costs of Schizophrenia in Switzerland.

BACKGROUND: Schizophrenia is a severe mental disorder that typically develops in early adulthood and becomes chronic in most cases. The disease is associated with elevated health care utilization, impaired functionality and the loss of life years and quality of life. The prevalence and costs of schizophrenia are not yet known for Switzerland. AIMS OF THE STUDY: This study aims to estimate the prevalence of schizophrenia in Switzerland and to assess its burden on patients, caregivers and society as a whole. METHODS: A hospital registry was combined with an outpatient physician survey and health insurance claims data to capture all patients living in the northern part of the canton of Zurich. Structured interviews with outpatient physicians were held to obtain information on outpatient care in private practices. Total costs included direct medical and nonmedical costs and lost production. All costs were calculated for the year 2012 from a societal perspective using a prevalence-based bottom-up approach. Intangible costs were expressed as quality-adjusted life years (QALY). Uncertainty and its sources were addressed in univariate and probabilistic sensitivity analyses. RESULTS: The point prevalence of schizophrenia in Switzerland was estimated at 0.39% of the population. The average costs of schizophrenia in 2012 were EUR 39,408 per patient. Lost production accounted for 64% (EUR 25,108) of the total cost of illness, direct medical costs for 24% (EUR 9,507) and care by relatives or in residential homes for the mentally ill for 12% (EUR 4,793). Inpatient hospital care amounted to EUR 6,242 per year or 66% of direct medical costs. DISCUSSION: The results show the high burden of schizophrenia on patients, caregivers and society. The prevalence estimate can be considered a lower bound because undiagnosed cases were not identified by our empirical strategy. The estimated costs are conservative because the costs of comorbidities were not considered. The strengths of this study are the full coverage of the sample region by a combination of different data sources and the careful evaluation of parameter uncertainty. The main limitation is the small sample size for the assessment of private practice outpatient care. IMPLICATIONS FOR HEALTH POLICIES AND FURTHER RESEARCH: The high costs of inpatient hospital care demonstrate the potential benefits of effectively preventing relapses associated with readmissions to inpatient care. Considering the high burden of lost production and the early onset of the disease, programs for reintegration into the labor market have high potential to reduce the costs of schizophrenia. Future research should address the evolution of costs over the disease course. This information would allow for assessing the cost-effectiveness of early detection and interventions that alter disease progression.

Cost-effectiveness of dabigatran for stroke prevention in atrial fibrillation in Switzerland.

OBJECTIVES: Atrial fibrillation is a major risk factor for ischemic stroke and anticoagulation therapy is indicated to reduce risk. Dabigatran is a new oral anticoagulant that does not require INR monitoring. This study evaluated the cost-effectiveness of dabigatran versus vitamin K antagonists for stroke prevention in atrial fibrillation in Switzerland. METHODS: A Markov model simulating the course of treatment and occurrence of clinical events in two treatment arms over the lifetime of patients was adapted to the Swiss context. The adaptation included the cost of anticoagulation therapy and clinical events in Switzerland. The cost of inpatient care was estimated on data of all inpatient hospital stays in 2008. The calculation of outpatient care costs was based on peer reviewed studies, expert interviews and local tariffs. RESULTS: Patients treated with dabigatran had a higher life expectancy and experienced more quality adjusted life years (QALY) while incurring higher costs than patients treated with vitamin K antagonists. The estimated incremental cost-effectiveness ratio (ICER) was CHF 25,108.‒ per QALY with 110 mg and CHF 9,702 per QALY with 150 mg of dabigatran. A sequential dosage scheme, in which 150 mg are administered up to the age of 80 years and 110 mg thereafter, resulted in an ICER of CHF 10,215 per QALY. A sensitivity analysis confirmed that these results are robust. CONCLUSIONS: Dabigatran can be considered cost-effective in comparison with vitamin K antagonists in the Swiss context. The higher drug cost of dabigatran is compensated by savings in INR monitoring, lower cost of clinical events and QALY-gains.

Cost of acute coronary syndrome in Switzerland in 2008.

QUESTIONS UNDER STUDY: To perform a cost-of-illness study of acute coronary syndrome (ACS) in Switzerland from a societal perspective, evaluating direct costs, production losses and intangible costs in terms of quality adjusted life years (QALYs) lost. METHODS: A bottom-up incidence-based approach was used. Data concerning patients with one or more ACS events were extracted from a national hospital database and from mortality statistics. Inpatient costs included acute care and rehabilitation. Outpatient costs included costs for ambulance, visits to GP and cardiologist, outpatient diagnostics, medication and rehabilitation. Production losses included absenteeism, permanent disability and premature death. Intangible costs were calculated on previously published QALY weights. Cost data were derived from official price lists, literature and experts. Future costs and QALYs lost were discounted. RESULTS: In 2008 14,955 patients experienced a total of 16,815 ACS events; 2,752 died as a consequence of these. The resulting 19,064 hospital stays had an average across-hospital length of stay of 9.1 days per patient. Total direct costs of ACS amounted to 630 Mio Swiss Francs (CHF) for society and CHF 462 Mio for health insurers. Total direct costs were dominated by costs of myocardial infarction: ST-elevation 45.8%, non-ST-elevation 35.8%. Production losses were CHF 519 Mio and intangible costs resulted in 49,878 QALYs lost. CONCLUSIONS: ACS causes considerable costs in terms of direct medical expenditures, lost production, suffering and premature death, even without taking into account costs for its chronic consequences such as congestive heart failure.