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.

Clostridioides difficile infection (CDI): A pan-European multi-center cost and resource utilization study, results from the Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI).

OBJECTIVES: Clostridioides difficile infection (CDI) is one of the leading nosocomial infections worldwide, resulting in a significantly increasing burden on the healthcare systems. However, Pan-European data about cost and resource utilization of CDI treatment do not exist. METHODS: A retrospective analysis within the Combatting Bacterial Resistance in Europe CDI project was conducted based on resource costs for inpatient treatment and productivity costs. Country-specific cost values were converted to EURO referred to 1 January, 2019 values. Differences in price levels for healthcare services among the participating countries were adjusted by using an international approach of the Organisation for Economic Co-operation and Development. As the study focused on patients with recurrent CDI, the observed study population was categorized into (a) patients with CDI but without CDI recurrence (case group), (b) patients with CDI recurrence (recurrence group), and (c) patients without CDI (control group). RESULTS: Overall, 430 hospitalized patients from 12 European countries were included into the analysis between July 2018 and November 2018. Distribution of mean hospital length of stay and mean overall costs per patient between the case group, recurrence group, and control group were as follows: 22 days (95% CI 17-27 days) vs. 55 days (95% CI 17-94 days) vs. 26 days (95% CI 22-31 days; p 0.008) and € 15 242 (95% CI 10 593-19 891) vs. € 52 024 (95% CI 715-103 334) vs. € 21 759 (95% CI 16 484-27 035; p 0.010), respectively. The CDI recurrence rate during the observational period was 18%. Change escalation in CDI medication (OR 3.735) and treatment in an intensive care unit (OR 5.454) were found to be the most important variables associated with increased overall costs of patients with CDI. CONCLUSIONS: Treatment of patients with recurrent CDI results in a significant burden. Prevention of CDI recurrences should be in focus of daily patient care to identify the most cost-effective treatment strategy.

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.

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.

Clinical and pharmacoeconomic evaluation of antifungal prophylaxis with continuous micafungin in patients undergoing allogeneic stem cell transplantation: A six-year cohort analysis.

BACKGROUND: Patients undergoing allogeneic stem cell transplantation (aSCT) are at high risk to develop an invasive fungal disease (IFD). Optimisation of antifungal prophylaxis strategies may improve patient outcomes and reduce treatment costs. OBJECTIVES: To analyse the clinical and economical impact of using continuous micafungin as antifungal prophylaxis. PATIENTS/METHODS: We performed a single-centre evaluation comparing patients who received either oral posaconazole with micafungin as intravenous bridging as required (POS-MIC) to patients who received only micafungin (MIC) as antifungal prophylaxis after aSCT. Epidemiological, clinical and direct treatment cost data extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut) were analysed. RESULTS: Three hundred and thirteen patients (97 and 216 patients in the POS-MIC and MIC groups, respectively) were included into the analysis. In the POS-MIC and MIC groups, median overall length of stay was 42 days (IQR: 35-52 days) vs 40 days (IQR: 35-49 days; p = .296), resulting in median overall costs of €42,964 (IQR: €35,040-€56,348) vs €43,291 (IQR: €37,281 vs €51,848; p = .993), respectively. Probable/proven IFD in the POS-MIC and MIC groups occurred in 5 patients (5%) vs 3 patients (1%; p = .051), respectively. The Kaplan-Meier analysis showed improved outcome of patients in the MIC group at day 100 (p = .037) and day 365 (p < .001) following aSCT. CONCLUSIONS: Our study results demonstrate improved outcomes in the MIC group compared with the POS-MIC group, which can in part be explained by a tendency towards less probable/proven IFD. Higher drug acquisition costs of micafungin did not translate into higher overall costs.

Principal-agent theory-based cost and reimbursement structures of isavuconazole treatment in German hospitals.

BACKGROUND: Isavuconazole (ISA) is a frequently used antifungal agent for the treatment of invasive fungal diseases (IFDs). However, hospital reimbursement data for ISA is limited. OBJECTIVES: The primary objective of this study was to analyse the different perspectives of relevant stakeholders and the (dis)incentives for the administration of ISA in Germany. To that aim, the health economic effects of using ISA from a hospital management perspective were analysed. PATIENTS/METHODS: Based on principal-agent theory (PAT), the perspectives of (a) the patient (principal) as well as (b) physicians, (c) pharmacists and iv. hospital managers (all agents) were analysed. For the evaluation of the cost-containment and reimbursement strategies of ISA, the German diagnosis-related group (G-DRG) system was used. RESULTS: Hospitals individually negotiating additional payments for innovative treatment procedures (zusatzentgelte [ZE]) within the G-DRG system is a key element of hospital management for the reduction of total healthcare expenditure. Our analysis demonstrated the beneficial role of ISA in healthcare resource utilisation, primarily due to a shortened overall length of hospital stay. Depending on underlying disease, coded G-DRG and ISA formulation, large differences in total reimbursement and the amount of ZE was shown. The PAT demonstrated disincentives for hospital managers to use innovative drugs. CONCLUSIONS: Based on the PAT, beneficial, detrimental and indifferent perspectives of different stakeholders regarding the usage of ISA were shown. A reduction of bureaucratic hurdles is needed in Germany for the extension of effective and innovative antifungal treatment strategies with ISA.

The economic burden of Clostridioides difficile infection in patients with hematological malignancies in the United States: A case-control study.

OBJECTIVE: The primary study aim was to describe all direct healthcare costs associated with Clostridioides difficile infection (CDI), both in and out of the hospital, in patients with hematologic malignancies in the United States. DESIGN: A retrospective analysis was conducted utilizing data from US databases of Truven Health Analytics. PATIENTS: We analyzed health insurance claims between January 2014 and December 2017 of patients diagnosed with hematological cancer: acute myeloid leukemia (AML), acute lymphoblastic leukemia, Hodgkin's lymphoma, and non-Hodgkin's lymphoma (NHL). METHODS: Patients with CDI after cancer diagnosis (CDI+, cases) were matched with patients without CDI reported (CDI-, controls). Matched cases and controls were compared to identify the CDI-associated costs in the 90 days following the onset of CDI. RESULTS: We matched 622 CDI+ patients with 11,111 CDI- patients. NHL (41.7%) and AML (30.9%) were the predominant underlying diseases in the CDI+ groups. During study period, the average time in-hospital of CDI+ patients was 23.1 days longer than for CDI- patients (P < 2×10-16). Overall, CDI onset increased costs of care by an average of US$57,159 per patient (P = 6×10-12), mainly driven by hospital costs. CONCLUSIONS: This study confirms the significant economic burden associated with CDI in the United States, especially in patients with hematological malignancies. These findings highlight the need for prevention of CDI in this specific patient population.

Chlorhexidine-containing dressings in the prevention of central venous catheter-related bloodstream infections: A cost and resource utilization analysis.

BACKGROUND: A recent study reported a reduction in probable/definite central venous catheter (CVC)-related bloodstream infections (CRBSIs) in neutropenic high-risk patients using CVC dressings with a chlorhexidine-containing gel pad. METHODS: Based on published data, a health-economic analysis was performed to analyze the economic effect of using CVC dressings with a chlorhexidine-containing gel pad compared to non-chlorhexidine control dressings. A micro-costing approach was used to determine CRBSI-related direct treatment cost factors. RESULTS: Between February 2012 and September 2014, 356 patients (178 patients in both groups) were analyzed. Distribution of probable and definite CRBSI in the chlorhexidine group and control group were 12 (7%) vs 18 (10%) and 9 (5%) vs 21 (12%), respectively (P = .011). Median overall length of stay (25 vs 27.5 days; P = .630) and days on treatment with antibacterials (10 vs 12 days; P = .140) were similar between the chlorhexidine and control groups. The most important cost driver in both groups was treatment on general ward (€4275 [US$ 5173], interquartile range [IQR]: €592 - €6504 [US$ 716 - US$ 7871] vs €4560 [US$ 5518], IQR: €1227 - €8567 [US$ 1485 - US$ 10,367]; P = .120), resulting in median overall direct treatment costs of €13,881 (US$ 16,798) [IQR: €10,922 - €25,457 (US$ 13,217 - US$ 30,807) vs €13,929 [US$ 16,856] [IQR: €11,295 - €23,561 (US$ 13,669 - US$ 28,512); P = .640]). CONCLUSION: Our study shows similar results in overall direct treatment costs, meaning that higher acquisition costs of chlorhexidine-containing dressings did not translate into higher costs. Expenses were primarily outweighed by a lower rate of probable/definite CRBSI and reduced associated costs.

Treatment of MRSA pneumonia: Clinical and economic comparison of linezolid vs. vancomycin - a retrospective analysis of medical charts and re-imbursement data of real-life patient populations.

Objectives: To supplement the data collected in randomized clinical trials, the present study in patients with methicillin resistant Staphylococcus aureus (MRSA) pneumonia was conducted to explore the clinical effectiveness of linezolid and vancomycin in a routine clinical setting. Further, the overall costs of the patients' stay in the intensive care unit (ICU) were compared. Methods: This was a retrospective analysis of medical and reimbursement data of adult patients who were treated for MRSA pneumonia with linezolid or vancomycin. Since the subjects were not randomly assigned to treatments, propensity score adjustment was applied to reduce a potential selection bias. Results: In total, 226 patients were included; 95 received linezolid and 131 received vancomycin as initial therapy for MRSA pneumonia. Switches to another antibiotic were observed in 4 patients (4.2%) receiving linezolid and in 23 patients (17.6%) receiving vancomycin (logistic regression analysis; odds ratio linezolid/vancomycin: 0.183; 95% confidence interval [CI]: 0.052-0.647; p<0.01). All-cause in-hospital mortality was also lower in patients receiving linezolid (22 patients [23.2%] vs. 54 patients [41.2%]) (logistic regression analysis; odds ratio linezolid/vancomycin: 0.351; 95% CI: 0.184-0.671; p<0.01). The analysis of the total costs of stay in ICU did not reveal any major differences between the two treatment groups (cost ratio linezolid/vancomycin: 1.29; 95% CI: 0.84-1.98; p=0.24). Conclusions: These findings confirm in a routine clinical setting that linezolid is a valuable therapeutic alternative to vancomycin for the treatment of MRSA pneumonia. However, prospective studies in real-life patient populations are warranted.

Economic evaluation of chronic lymphocytic leukemia from a hospital management perspective.

OBJECTIVES: Treatment of chronic lymphocytic leukemia (CLL) is currently undergoing dramatic changes. We analyzed economic risks in hospitalized patients with CLL from a management perspective. METHODS: One hundred and twelve patients with CLL hospitalized in 2013 and 2014 at the University Hospital of Cologne were analyzed. To assess profit margins (PMs) per case, diagnosis-related group (DRG) reimbursement data were merged with an internal cost accounting scheme depending on age, prognostic factors, and DRG key performance indicators. RESULTS: In 112 patients, 284 cases coded by 19 different DRG with strongly fluctuating cost revenue ratios were found with an overall negative PM of €137 147. The DRG R61H was identified as the one most commonly coded (174 cases, 61.3%) with a deficit per case of €814. Subanalysis demonstrated that the payments were not cost covering due to excessive length of stay and staff costs. Significant differences in PM per case concerning age, length of stay and number of operation and procedure key (OPS) codes (P < 0.05) were found. CONCLUSION: In our research-driven tertiary care hospital, inpatient treatment of patients with CLL is not cost covering. This analysis demonstrates the need for novel care/reimbursement structures in CLL. From a hospital management perspective, cost revenue controlling is crucial to avoid major economic risks.

A cost and resource utilization analysis of micafungin bridging for hemato-oncological high-risk patients undergoing allogeneic stem cell transplantation.

BACKGROUND: Intravenous bridging strategies increase exposure of antifungal prophylaxis in high-risk hematological patients. The cost-effectiveness of such strategies has not been analyzed. METHODS: A recent study compared the impact of oral posaconazole (POS) and oral posaconazole with intravenous micafungin bridging (POS-MIC) as prophylactic antifungal regimens in patients undergoing allogeneic stem cell transplantation (aSCT). Based on data from the Cologne Cohort of Neutropenic Patients (CoCoNut), a health economic evaluation of direct treatment costs was performed to analyze the economic impact of micafungin bridging. Analysis was undertaken based on current guidelines for the German societal perspective with an annual discount rate of 5%, whereby indirect costs were disregarded due to the severity of the underlying disease. Sensitivity analysis of cost calculation with different discount rates was performed to improve robustness of our health economic evaluation. RESULTS: A retrospective case-control analysis of patients undergoing aSCT between 05/2006 and 07/2011 was performed; 106 patients each in the POS and POS-MIC group were included. In the POS and POS-MIC group, mean costs per patient for the treatment on bone marrow transplant ward were €27,228 (95% CI: €24,932-€29,525) vs. €27,894 (95% CI: €26,414-€29,375; P = 0.629), for diagnostic measures €2124 (95% CI: €1823-€2425) vs. €1269 (95% CI: €1168-€1370; P ≤ 0.001), for laboratory findings €10,612 (95% CI: €9681-€11,544) vs. €8836 (95% CI: €8198-€9475; P = 0.002), and for overall antifungal treatment €6105 (95% CI: €4703-€7508) vs. €6943 (95% CI: €5393-€8493; P = 0.428), resulting in mean overall costs per patient of €60,304 (95% CI: €53,969-€66,639) vs. €58,089 (95% CI: €51,736-64,442; P = 0.625). CONCLUSIONS: Our health economic evaluation shows micafungin bridging in aSCT patients did not result in excess cost. Higher acquisition costs of antifungal prophylaxis were balanced by a reduced incidence of possible IFD and lower costs for empirical, preemptive, and targeted antifungal therapy as well as lower costs for diagnostic measures and laboratory tests in the micafungin bridging group.

Treatment cost development of patients undergoing remission induction chemotherapy: a pharmacoeconomic analysis before and after introduction of posaconazole prophylaxis.

Prior clinical trials have demonstrated efficacy and effectiveness of posaconazole in the prophylaxis of invasive fungal diseases in high-risk patients. Controversy exists about the cost-effectiveness of this approach. We performed an analysis comparing the direct costs of posaconazole prophylaxis against polyene mouthwash (thrush) prophylaxis in patients with acute myelogenous leukaemia (AML). Data of AML patients receiving remission-induction chemotherapy were extracted from the CoCoNut (Cologne Cohort of Neutropenic Patients) database to compare hospital costs of patients before (2003-2005) and after (2006-2008) introduction of posaconazole prophylaxis. Treatment on general ward, intensive care unit (ICU), mechanical ventilation, diagnostic procedures, and all anti-infectives were calculated. Patient groups were well matched according to age, gender and duration of neutropenia. The mean costs per patient in the posaconazole group (n = 76) and the polyene mouthwash group (n = 81) were €21 040 (95% confidence interval (CI): €18 204-€23 876) and €23 169 (95% CI: €19 402-€26 937) per patient. Antifungal treatment costs were €4580 (95% CI: €3678-€5482) and €4019 (95% CI: €2825-€5214). Duration on the ICU was 2582 (95% CI: 984.1-4181.7) and 5517 (95% CI: 2206-8827.3) min. In our hospital, primary antifungal prophylaxis by posaconazole was cost-effective. There was a trend towards cost savings, which was primarily caused by a shorter overall length of stay and the less frequent ICU treatment.