Cost-effectiveness analysis of transplant-ineligible relapsed or refractory diffuse large B-cell lymphoma treatment options-Experience of the efficiency frontier approach.

OBJECTIVES: The treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) changed remarkably since the European Medicines Agency-approved chimeric antigen receptor T-cell (CAR-T) therapies (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tisagenlecleucel [tisa-cel]) for the third-line onwards (3+L), and targeted therapies (polatuzumab vedotin-bendamustine-rituximab [pola-BR], tafasitamab-lenalidomide [Tafa-L]) for the second-line (2L) onwards. As associated rising treatment costs represent an economic burden, the cost-effectiveness of transplant-ineligible R/R DLBCL interventions was assessed from a German healthcare payer's perspective, using the efficiency frontier (EF) approach. METHODS: A systematic literature review was performed to determine the clinical benefit concerning median overall survival (OS) of bendamustine-rituximab (BR), rituximab-gemcitabine-oxaliplatin (R-GemOx), axi-cel, liso-cel, tisa-cel, pola-BR, and Tafa-L. First-year treatment costs (drug and medical services costs) were calculated. Results were merged on two-dimensional graphs illustrating 2L and 3+L EFs. RESULTS: Second-line EF is formed by BR (median OS 11.49 months, €23 958) and Tafa-L (45.7, €104 541), 3+L EF is formed by R-GemOx (12.0, €29 080), Tafa-L (15.5, €104 541), and axi-cel (18.69, €308 516). These interventions build the respective cost-effectiveness thresholds for novel interventions. CONCLUSIONS: Using the EF approach, the currently most cost-effective interventions (based on cost-effectiveness ratios) in the indication of R/R DLBCL were identified to guide international reimbursement decisions.

Health-economic modelling of cost savings due to the use of rezafungin based on a German cost-of-illness study of candidiasis.

Objective: Candida species are responsible for fungal diseases and the development of nosocomial bloodstream infections. Treatment is resource-intensive and economically challenging for healthcare systems. Cost analyses of drugs against candidiasis, such as rezafungin, are thus of great interest to healthcare payers. Methods: We conducted a cost-of-illness study of patients with Candida infections based on real-word data of the Department I of Internal Medicine, University Hospital Cologne (Germany) between 2016 and 2021. Health-economic parameters were analysed to describe the economic impact of Candida infections. Potential cost savings due to the administration of rezafungin were modelled for patients with invasive candidiasis or candidaemia based on a 5 day reduction of ICU length of stay (LOS) shown by the STRIVE study. Results: We found 724 cases (652 patients) with Candida infections, of which 61% received ICU treatment (n = 442) and 29% were mechanically ventilated (n = 207). Twenty-six percent died during hospitalization (n = 185). Median LOS was 25 and 15 days, on normal wards and ICU, respectively. Median total treatment costs per case accounted for €22 820. Based on the ICU LOS reduction, the retrospective model showed a median cost-saving potential of €7175 per hospital case with invasive candidiasis or candidaemia. Accumulated cost savings for 37 patients of €283 335 were found. Conclusions: Treatment of candidiasis is cost intensive due to increased hospital LOS. The ICU LOS reduction rezafungin showed in STRIVE would lead to sustainable cost savings.

Health economic analysis of patients treated with isavuconazole in a German comprehensive cancer centre.

BACKGROUND: Invasive fungal diseases (IFD) are life-threatening and demand timely and appropriate treatment. Research showed that isavuconazole treatment positively affects clinical outcome and length of hospital stay (LOS). OBJECTIVES: The aim of this study was to assess the hospital costs of patients diagnosed with IFD and treated with isavuconazole using real-world data from a German cancer centre. PATIENTS/METHODS: Data and LOS collected from Jan-2016 to Jun-2021 at Department I of Internal Medicine, University Hospital Cologne were retrieved. Case-related resources consumed during the hospital stay across isavuconazole routes of administration (oral, parenteral, and mixed administration) were identified, quantified, valued and compared via a cost analysis that adopted the healthcare payer perspective. RESULTS: In total, 101 cases with isavuconazole treatment were identified (oral: n = 22, 21.8%; parenteral: n = 59, 58.4%; mixed: n = 20, 19.8%). Median total LOS was greater in the mixed group (46.5 days; p = .009). Median ICU LOS and ventilation duration were both longest in the parenteral-only group (16 days, p = .008; 224 h, p = .003). Invasive aspergillosis was the most frequent isavuconazole indication (n = 86, 85.2%). Average hospital costs were highest in the mixed group (€ 101,226). The median overall costs of cases treated with isavuconazole was € 52,050. CONCLUSIONS: Treating IFD is resource intensive, often requires intensive care and implies high rates of in-hospital mortality. Our study emphasises the high hospital treatment costs and thus the need for reimbursement systems to enable live-saving costly treatments.

Last Resort Antibiotics Costs and Reimbursement Analysis of Real-Life ICU Patients with Pneumonia Caused by Multidrug-Resistant Gram-Negative Bacteria in Germany.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) cause serious infections and aggravate disease progression. Last resort antibiotics are effective against MDR-GNB and are reimbursed by flat rates based on German diagnosis-related groups (G-DRG). From a hospital management perspective, this analysis compared hospital reimbursement for last resort antibiotics with their acquisition costs to outline potential funding gaps. Retrospective analyses based on medical charts and real-life reimbursement data included patients with pneumonia due to MDR-GNB treated in intensive care units (ICU) of a German tertiary care hospital (University Hospital Cologne) between January 2017 and December 2020. Drug-associated hospital reimbursement of G-DRG was compared with drug acquisition costs based on preliminarily approved last resort antibiotics (cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-cilastatin-relebactam) according to label. Funding gaps were determined for the treatment of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and mixed infections, respectively. Most of the 31 patients were infected with Enterobacterales (n = 15; 48.4%) and P. aeruginosa (n = 13; 41.9%). Drug-associated G-DRG reimbursement varied from 44.50 EUR (mixed infection of P. aeruginosa and Enterobacterales) to 2265.27 EUR (P. aeruginosa; mixed infection of P. aeruginosa and Enterobacterales). Drug acquisition costs ranged from 3284.40 EUR in ceftazidime-avibactam (minimum duration) to 15,827.01 EUR for imipenem-cilastatin-relebactam (maximum duration). Underfunding was found for all MDR-GNB, reaching from 1019.13 EUR (P. aeruginosa; mixed infection of P. aeruginosa and Enterobacterales) to 14,591.24 EUR (Enterobacterales). This analysis revealed the underfunding of last resort antibiotics in German hospital treatment. Insufficient reimbursement implies less research in this field, leading to a more frequent use of inappropriate antibiotics. The cycle closes as this contributes to the development of multi-drug resistant bacteria.

Health economic analysis of third-line interventions in diffuse large B-cell lymphomas in Germany: applying the efficiency frontier.

BACKGROUND: In the past decades, highly innovative treatments in the field of diffuse large B-cell lymphoma (DLBCL) became available in clinical practice. The aim of this study was to assess the cost-benefit relation of third-line interventions in DLBCL from a German payer perspective. METHODS: Clinical benefit of allogeneic stem cell transplantation (alloSCT), chimeric antigen receptor T cells therapy (CAR T) [tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel)] and best supportive care (BSC) was assessed in terms of median overall survival (median OS) derived from a systematic literature review in PubMed. Real-world treatment costs were retrieved from the university hospitals Cologne and Hamburg-Eppendorf. The cost-benefit relation was analysed using the efficiency frontier concept. RESULTS: Median OS varied from 6.3 months in BSC to 23.5 months in CAR T (axi-cel), while median real-world treatment costs ranged likewise widely from €26,918 in BSC to €340,458 in CAR T (axi-cel). Shown by the efficiency frontier, alloSCT and axi-cel were found as most efficient interventions. CONCLUSION: The efficiency frontier supports the pricing of innovative therapies, such as third-line interventions in DLBCL, in relation to appropriate comparators. Yet, studies with longer follow-up periods are needed to include studies with unreached median OS and to reflect experiences gained with CAR T in clinical practice.

A cost of illness study of COVID-19 patients and retrospective modelling of potential cost savings when administering remdesivir during the pandemic "first wave" in a German tertiary care hospital.

PURPOSE: First detected in China in 2019, the novel coronavirus disease (COVID-19) has rapidly spread globally. Since then, healthcare systems are exposed to major challenges due to scarce personnel and financial resources. Therefore, this analysis intended to examine treatment costs of COVID-19 inpatients in a German single centre during the first pandemic wave in 2020 from a healthcare payer perspective. Potential cost savings were assessed considering the administration of remdesivir according to the European Medicines Agency label. METHODS: A retrospective medical-chart review was conducted on COVID-19 patients treated at University Hospital Cologne, Germany. Patients were clustered according to an eight-category ordinal scale reflecting different levels of supplemental oxygen. Potential cost savings due to the administration of remdesivir were retrospectively modelled based on a reduced length of stay, as shown in the Adaptive COVID-19 Treatment Trial. RESULTS: 105 COVID-19 patients were identified. There was wide variability in the service data with median treatment costs from EUR 900 to EUR 53,000 per patient, depending on major diagnosis categories and clinical severity. No supplemental oxygen was needed in 40 patients (38.1%). Forty-three (41.0%) patients were treated in intensive-care units, and 30 (69.8%) received invasive ventilation. In our model, in-label administration of remdesivir would have resulted in costs savings of EUR 2100 per COVID-19 inpatient (excluding acquisition costs). CONCLUSION: We found that COVID-19 inpatients suffer from heterogeneous disease patterns with a variety of incurred G-DRG tariffs and treatment costs. Theoretically shown in the model, financial resources can be saved by the administration of remdesivir in eligible inpatients.

A budget impact analysis of bezlotoxumab versus standard of care antibiotics only in patients at high risk of CDI recurrence from a hospital management perspective in Germany.

BACKGROUND: Clostridioides difficile infection (CDI) is one of the leading nosocomial infections, resulting in increased hospital length of stay and additional treatment costs. Bezlotoxumab, the first monoclonal antibody against CDI, has an 1 A guideline recommendation for prevention of CDI, after randomized clinical trials demonstrated its superior efficacy vs. placebo. METHODS: The budget impact analysis at hand is focused on patients at high risk of CDI recurrence. Treatment with standard of care (SoC) + bezlotoxumab was compared with current SoC alone in the 10 most associated Diagnosis Related Groups to identify, analyze, and evaluate potential cost savings per case from the German hospital management perspective. Based on variation in days to rehospitalization, three different case consolidation scenarios were assessed: no case consolidation, case consolidation for the SoC + bezlotoxumab treatment arm only, and case consolidation for both treatment arms. RESULTS: On average, the budget impact amounted to € 508.56 [range: € 424.85 - € 642.19] for no case consolidation, € 470.50 [range: € 378.75 - € 601.77] for case consolidation in the SoC + bezlotoxumab treatment arm, and € 618.00 [range: € 557.40 - € 758.41] for case consolidation in both treatment arms. CONCLUSIONS: The study demonstrated administration of SoC + bezlotoxumab in patients at high risk of CDI recurrence is cost-saving from a hospital management perspective. Reduced length of stay in bezlotoxumab treated patients creates free spatial and personnel capacities for the treating hospital. Yet, a requirement for hospitals to administer bezlotoxumab is the previously made request for additional fees and a successful price negotiation.

Reimbursement of innovative pharmaceuticals in English and Spanish hospitals-The example of isavuconazole.

BACKGROUND: Kron et al (Mycoses, 64, 2021, 86) found cost savings for the use of the innovative pharmaceutical isavuconazole in the inpatient setting in Germany (Bismarck-based healthcare system). Little is known about the reimbursement of innovative pharmaceuticals in the inpatient setting of Beveridge-based healthcare systems. OBJECTIVES: The aim of this study was to evaluate the market access process and reimbursement of isavuconazole, exemplary for innovative pharmaceuticals, in England and Spain. PATIENTS/METHODS: Market access processes of both countries were described. Focussing on typical patient clusters for isavuconazole treatment, reimbursement data regarding inpatients with (i) allogeneic haematopoietic stem cell transplantation or (ii) acute myeloid leukaemia was considered. Data were publicly available and of high topicality (England 2020/2021, Spain 2018). Discounting and a currency conversion to Euro were applied. RESULTS: This study showed that market access processes of both countries are broadly similar. Further, full reimbursement of isavuconazole as an innovative pharmaceutical may lead to reduction in resource utilisation. Without medication costs, isavuconazole can thus result in cost savings for both patient clusters due to a reduction in length of stay. CONCLUSIONS: Expenses for innovative pharmaceuticals may be balanced or even lead to cost savings due to a reduction in length of stay. The latter contributes to a greater patient benefit. For both healthcare system, the analyses highlighted drugs' cost-effectiveness and assessing its added value into reimbursement decisions is highly relevant.

Economic Impact of the Introduction of Outpatient Medical Specialist Care (ASV) of Gastrointestinal Cancer Patients from a German Hospital Management Perspective.

INTRODUCTION: The treatment of cancer patients in Germany is characterized by sectoral separation of the in- and outpatient care accompanied by 2 separate reimbursement systems. By introducing the Guideline of Outpatient Medical Specialist Care in accordance with §116b SGB V (ASV) in 2014, the German legislation empowers office-based physicians and hospitals to jointly provide medical care in the ambulatory setting. METHODS: A 1-year period each before and after the introduction of ASV was compared by means of data from the Center for Integrated Oncology Cologne at the University Hospital of Cologne. Only adults with a reliable diagnosis of gastrointestinal tumor (GIT) were considered. RESULTS: Overall, 1,872 cases were considered in the analysis showing significant (p < 0.001) higher median values of revenues across ICD-subgroups for ASV (EUR 427.46) compared to Ambulatory Treatments in Hospitals (EUR 234.21). The exemplary analysis of revenues in neoplasms of the pancreas shows EUR 173.69 on average which are only invoiceable through ASV: flat rate incl. surcharges (EUR 117.79; 68%), structure lump sum (EUR 29.49; 17%), positron-emission tomography (PET)/CT (EUR 13.53; 18%), and ASV consultation hour (EUR 12.89; 7%). DISCUSSION/CONCLUSION: ASV leads to significant higher revenues across different ICD-subgroups for patients suffering from severe GIT. The collaboration of hospital and office-based physicians ensures patient-centered care with accumulated expertise and avoidance of double examinations. Thus, the inclusion of additional services in the Uniform Value Scale (invoiceable for ASV) is legitimated and enables cost-covering care for the involved parties.