Pharmacoeconomic issues in stem cell mobilization.

BACKGROUND: recently, stem cell mobilization has made dramatic progress, that ended up in an increasing number of aphereses at target for autologous peripheral stem cell transplantation (ASCT). The aim of this research is investigating the cost-effectiveness of stem cell mobilization. METHODS: a narrative review of the literature was carried out, searching for primary contributions written in English and published during 2000-2023 on cost-effectiveness analysis (CEA) of stem cell mobilization in patients entitled to ASCT. The PubMed database was searched with the following sets of keywords: cost-effectiveness AND apheresis AND myeloma (PubMed_1); cost-effectiveness AND stem cell mobilization (PubMed_2). Articles included in the analysis were assessed via two different checklists. RESULTS: sixty-six entries were retrieved. Five out of 66 (PubMed_1: 4 out 17; PubMed_2: 1 out of 49), 4 CEAs and 1 cost-utility analysis (CUA) fit the research goal. Four out of 5 contributions proved to be in line with most of the items included in the two assessment grids. However, the most relevant missing features in some of the included contributions were: study perspective, healthcare resources valuation, and sensitivity analyses. DISCUSSION: most of the articles included in this research show that chemotherapy-free stem cell mobilization is cost-effective according to different standpoints. Future health economic research on this topic should establish local threshold values for incremental apheresis at target and explore the heterogeneity of CEA (and CUA) to determine oncohaematological diseases and patient categories for which chemotherapy-free stem cell mobilization is cost-effective in different healthcare systems, given local budget constraints.

Full cost of diagnostic pathology for lung carcinoma in Italy: results from four Pathology Units.

Objective: To calculate the full cost of diagnostic pathology tests for Non-Small Cell Lung Cancer (NSCLC) across four Italian Pathology Units. Methods: Pathology Units were located in private (2) and public (2) hospitals distributed across the Italian territory (North: 2; Centre: 1; South: 1). Pathologists provided via questionnaire data on tests on NSCLC samples along with the identification and quantification of the necessary healthcare resources (diagnostic technologies, laboratory instruments and personnel). Resources were valued according to hospital-specific unit, yearly and hourly costs (disposables; technologies; professional clusters). Results: The full cost per NSCLC tissue sample included histopathological immunophenotypic and required molecular analysis. Overall, it reached € 659.77 and it was mainly composed of direct costs (77.69%). The processing of a NSCLC tissue sample was labour intensive, as a relevant share of the full cost (44.98%) was actually due to personnel costs, with laboratory technicians, biologists and pathologist driving this finding (17.09%,12.43% and 10.81%, respectively). Conclusions: The results of this research can facilitate the negotiation of new dedicated tariffs for NSCLC sample processing with the national or local third party-payers.

Cost-utility analysis of teriflunomide in naïve vs. previously treated patients with relapsing-remitting multiple sclerosis in Italy.

BACKGROUND: Multiple sclerosis (MS) accounts for 176 cases per 100,000 inhabitants (female/male ratio = 2:1) in Italy. For most of the patients (67%), the disease course is relapsing-remitting MS (RRMS). OBJECTIVE: To compare the costs and quality-adjusted life years (QALYs) of teriflunomide in RRMS naïve patients vs. RRMS patients previously treated (experienced) with other disease-modifying therapies in Italy. METHODS: A four health states Markov model-supported cost-utility analysis (CUA) covering a 7-year timespan through annual cycles was developed, following the healthcare sector and the societal viewpoints. Part of the parameters that populated the Markov model was obtained from a questionnaire administered to four primary Italian MS centres. Costs of healthcare and non-healthcare resources, expressed in euro (€) 2019, and QALYs were discounted at 3% real social discount rate. One-way, scenario and probabilistic sensitivity analyses tested the uncertainty of the baseline findings. RESULTS: Baseline CUA shows that teriflunomide in RRMS naïve patients is strongly dominant vs. experienced patients (healthcare sector perspective: - €1042.68 and + 0.480 QALYs; societal perspective: - €6782.81 and + 0.480 QALYs). Sensitivity analyses confirmed the robustness of the baseline results. CONCLUSION: Teriflunomide in RRMS naïve vs. experienced patients is cost-effective and possibly strongly dominant from both the healthcare sector and the society viewpoints in Italy. Our findings need further confirmation from real-world studies.

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.

Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis.

Prior researches have suggested that home-based subcutaneous immunoglobulin (SCIG) is equally effective and can be less expensive than hospital-based intravenous immunoglobulin (IVIG) in treating chronic inflammatory demyelinating polyneuropathy (CIDP) patients. This economic evaluation aims at comparing costs of SCIG vs IVIG for CIDP patients in Italy. A 1-year model-based cost-minimization analysis basically populated via neurologists' opinion was undertaken from a societal perspective. Health care resources included immunoglobulin; drugs for premedication and complications (rash, headache, and hypertension) management; time of various health care professionals; pump for SCIG self-administration; infusion disposables. Non-health care resources encompassed transport and parking; losses of working and leisure time for patients and caregivers. Unit or yearly costs for resources valuation were mainly obtained from published sources. Costs were expressed in Euro () 2013. An extensive one-way sensitivity analysis (OWSA) and a scenario SA tested the robustness of the base case findings. Overall costs per patient amount to 49,534.75 (SCIG) and 50,895.73 (IVIG); saving in favour of SCIG reaches 1360.98. For both SCIG and IVIG, the cost driver was immunoglobulin (94.06 vs 86.06 % of the overall costs, respectively). Sensitivity analyses confirmed the consistency of the baseline results. SCIG may be a cost-saving therapy for Italian CIDP patients.

Impact of extending device longevity on the long-term costs of implantable cardioverter-defibrillator therapy: a modelling study with a 15-year time horizon.

AIMS: To determine the long-term costs of extending device longevity in four patient populations requiring a single-chamber implantable cardioverter-defibrillator (ICD) or requiring cardiac resynchronization therapy with defibrillation (CRT-D) device over a 15-year time window. METHODS AND RESULTS: We considered patient populations with an accepted indication for a single-chamber ICD for prevention of sudden cardiac death in the context of preserved (Population A) or impaired (Population B) left ventricular function; or with indication for a CRT-D device in the context of heart failure in New York Heart Association class II (Population C) or III (Population D). Expected patient survival and a cost analysis, including the cost of complications, was undertaken from a hospital perspective. Extended device longevity of 5 vs. 9 years for ICDs (Populations A and B); 4 vs. 7 years for CRT-Ds (Populations C and D) were considered. Over a 15-year time horizon, total, yearly, and per diem savings, per patient, from extending ICD longevity to 9 years were €10 926.91, €728.46, and €1.99 for Population A, and €7661.32, €510.75, and €1.40 for Population B. Total, yearly, and per diem savings from extending CRT-D longevity to 7 years were €13 630.38, €908.69, and €2.49 for Population C, and €10 968.29, €731.22, and €2.00 for Population D. Avoidance of a generator replacement amounted up to 46.6-62.5% of the saving. CONCLUSION: Extending device longevity has an important effect on the long-term cost of device therapy, both for ICD and CRT-D. This has important implications for device choice.

Inebilizumab for neuromyelitis optica spectrum disorders in Italy: a budget impact model.

BACKGROUND: The Italian National Health Service (INHS) has recently reimbursed the monoclonal antibody inebilizumab as a second line monotherapy after rituximab (RTX) use for neuromyelitis optica spectrum disorders (NMOSD) patients ≥ 18 years anti-aquaporin 4 antibody-immunoglobulin G positive, who experienced a relapse in the last year or cannot receive RTX, if incident patients. Other INHS-reimbursed drugs for NMOSD treatment are satralizumab, eculizumab and, off-label, besides RTX, ocrelizumab, tocilizumab, and immunosuppressants. RESEARCH DESIGN AND METHODS: A 3-year (2023-2025) prevalence-based budget impact model following the INHS viewpoint compared the costs and the NMOSD attacks without (1st scenario) and with inebilizumab (2nd scenario). The epidemiology of NMOSD, and the INHS-funded healthcare resources (drugs and their administration; specialist visits; hospitalizations due to drug-related adverse events and NMOSD attacks) were obtained from the literature. One-way, threshold value and scenario sensitivity analyses investigated the robustness of the baseline findings. RESULTS: During 2023-2025 inebilizumab saves the INHS €8,373,125.13 (1st scenario: €176,770,028.63; 2nd scenario: €168,396,903.50) and 12.74 NMOSD attacks (1st scenario: 213.94; 2nd scenario: 201.19). Sensitivity analyses confirmed the robustness of the baseline results. CONCLUSION: Inebilizumab reduces the INHS expenditure for NMOSD drugs. Future research should explore the cost-effectiveness of inebilizumab vs other NMOSD-targeting drugs in Italy.

A latanoprost cationic emulsion (STN1013001) vs. other latanoprost formulations (Latanoprost) in open angle glaucoma/ocular hypertension and ocular surface disease: an Italian cost-utility analysis.

BACKGROUND: STN1013001 is an innovative latanoprost cationic emulsion for open-angle glaucoma/ocular hypertension (OAG/OHT) and ocular surface disease (OSD). METHODS AND FINDINGS: A 5-year, 7 health states, 1-year cycle early Markov model-supported cost-utility analysis (CUA) of STN1013001 vs. other latanoprost formulations (Latanoprost) followed the Italian National Health Service (INHS) perspective.One-way, probabilistic and scenario sensitivity analyses tested the uncertainty of the baseline results. Value of information analysis (VOIA) investigated the potential cost-effectiveness of collecting further evidence. RESULTS: Over 5 years, the Markov model-supported CUA predicts STN1013001 to be potentially highly cost-effective vs. Latanoprost (+€57.60 cost at €2020 values; +0.089 Quality-Adjusted Life Years).The Incremental Cost-Utility Ratio (€647.65) falls well below the lower limit of the acceptability range proposed for Italy (€25,000-€40,000).Sensitivity analyses confirmed the robustness of the baseline findings. VOIA highlighted that further information might only be cost-effective for OAG/OHT utilities and OSD-related disutility. CONCLUSION: STN1013001 is potentially highly cost-effective and strongly dominant vs. Latanoprost for OAG/OHT+OSD patients from the INHS perspective. These findings should be re-assessed using the data from the ongoing Phase III trial (NCT04133311) comparing the efficacy and safety of STN1013001 vs. Latanoprost and with future real-world CUAs upon the availability of STN1013001 on the Italian market.

Cost-Utility Analysis of STN1013001, a Latanoprost Cationic Emulsion, versus Other Latanoprost Formulations (Latanoprost) in Open-Angle Glaucoma or Ocular Hypertension and Ocular Surface Disease in France.

Purpose: To investigate the cost utility of STN1013001, a latanoprost cationic emulsion, versus Latanoprost in patients with open-angle glaucoma or ocular hypertension (OAG/OHT) and concomitant ocular surface disease (OSD) in France. Methods: An early Markov model, including 7 health states and a 1-year cycle length, was developed to estimate the cost utility of STN1013001 versus Latanoprost from the French health system perspective over a 5-year time horizon. The model was populated with pooled data (treatment adherence, quality of life, disease progression, and resource utilization) collected, via a questionnaire, from a convenience sample of 5 French glaucoma specialists. Remaining data were retrieved from published sources. Half-cycle correction and 2.5% real social discount rate were applied to costs (in €2020), life years saved (LYS), and quality-adjusted life years (QALYs). The incremental cost-utility ratio (ICUR) was contrasted against the informal willingness-to-pay (WTP) range for incremental LYS or QALY gained (€30,000-€50,000) suggested for France. One-way and probabilistic sensitivity analyses tested the robustness of the baseline ICUR. Results: Over a 5-year time horizon, STN1013001 resulted in an incremental 0.35 QALYs gained at an incremental cost of €7.39 compared to Latanoprost, resulting in an ICUR of €21.26. This is well below the lower limit of the unofficial WTP range proposed for France. Sensitivity analyses confirmed the robustness of the baseline results. Conclusion: Once on the market, STN1013001 will provide the French health system with a cost-effective treatment versus Latanoprost for OAG/OHT + OSD patients. These results should be confirmed by future economic evaluations carried out alongside empirical trials.

Cost-Utility Analysis of a Latanoprost Cationic Emulsion (STN1013001) versus Other Latanoprost in the Treatment of Open-Angle Glaucoma or Ocular Hypertension and Concomitant Ocular Surface Disease in Germany.

PURPOSE: This study aimed to estimate the cost-utility and economic value of STN1013001, a latanoprost cationic emulsion vs other latanoprost formulations (henceforth latanoprost) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and concomitant ocular surface disease (OSD) in Germany. METHODS: An early 5-year Markov model-supported cost-utility analysis was performed to estimate costs, quality-adjusted life years (QALYs) and life-years saved (LYS) for STN1013001 vs latanoprost from the German health system perspective. The model included seven mutually exclusive health states and adopted a 1-year cycle length. The model was populated with pooled data derived, by means of a questionnaire, from a convenience sample of five German glaucoma specialists. Remaining data were derived from published sources. Data provided by the ophthalmologists included annual treatment adherence probabilities, utility values and resource utilization. The half-cycle correction as well as a discount rate of 3.0% per year were applied to costs (expressed in €2020), life-year saved (LYS) and QALYs. The incremental cost-utility ratio (ICUR) was contrasted against the informal willingness-to-pay (WTP) threshold for incremental LYS saved or QALY gained (€30,000) proposed for Germany. One-way and probabilistic sensitivity analyses (OWSA; PSA) tested the robustness of the base case ICUR. RESULTS: Over the 5-year time horizon, STN1013001 strongly dominates latanoprost as it is less costly (€1003.65 vs €1145.37; -12.37%) and produces more QALYs (2.612 vs 2.365; +10.44%) per notional patient. Baseline findings were robust against all the variations included in OWSA. PSA shows that STN1013001 has a 100% probability of being cost-effective vs Latanoprost at each WTP threshold for incremental QALY gained. CONCLUSION: Once on the market, STN1013001 will provide a cost-effective and possibly strongly dominant therapy vs latanoprost for OAG/OHT+OSD patients from a German health system perspective. Future empirical research should confirm these findings.

Chemotherapy-based versus chemotherapy-free stem cell mobilization (± plerixafor) in multiple myeloma patients: an Italian cost-effectiveness analysis.

Given the availability and efficacy of the mobilizing agent plerixafor in augmenting hematopoietic progenitor cell mobilization with granulocyte colony-stimulating factor (G-CSF), there is a strong case for comparing the cost-effectiveness of mobilization with G-CSF + cyclophosphamide versus G-CSF alone. This study investigated the cost and effectiveness (i.e., successful 4 million-CD34+ collection) of G-CSF alone versus high-dose cyclophosphamide (4 g/m2) + G-CSF mobilization (± on-demand plerixafor) in patients with multiple myeloma (MM) eligible for autograft in Italy. A decision tree-supported cost-effectiveness analysis (CEA) model in MM patients was developed from the societal perspective. The CEA model compared G-CSF alone with cyclophosphamide 4 g/m2 + G-CSF (± on-demand plerixafor) and was populated with demographic, healthcare and non-healthcare resource utilization data collected from a questionnaire administered to six Italian oncohematologists. Costs were expressed in Euro (€) 2019. The CEA model showed that G-CSF alone was strongly dominant versus cyclophosphamide + G-CSF ( ± on-demand plerixafor), with incremental savings of €1198.59 and an incremental probability of a successful 4 million-CD34+ apheresis (+0.052). Sensitivity analyses confirmed the robustness of the base-case results. In conclusion, chemotherapy-free mobilization (± on-demand plerixafor) is a "good value for money" option for MM patients eligible for autograft.

AbobotulinumtoxinA and rehabilitation vs rehabilitation alone in post-stroke spasticity: A cost-utility analysis.

OBJECTIVE: To investigate costs and quality-adjusted life years of rehabilitation combined with abobotulinumtoxinA (aboBoNT-A) (rehab/aboBoNT-A) vs rehabilitation alone (rehab) in post-stroke spasticity in Italy. DESIGN: Based on both Italian National Health Service and societal perspectives, a 2-year cost-utility analysis model was performed. Subject/patients: The cost-utility analysis model considered hypothetical patients. METHODS: The cost-utility analysis model was populated with data concerning demographics, disease severity, healthcare and non-healthcare resource consumption. Data were collected via a questionnaire administered to 3 highly experienced Italian physiatrists (864 out of 930 post-stroke spasticity patients on rehab/aboBoNT-A in total). Costs are expressed in Euro (€) based on the year 2018. RESULTS: The cost to society (rounded to the nearest whole €) was €22,959 (rehab/aboBoNT-A) vs €11,866 (rehab). Italian National Health Service-funded cost was €7,593 (rehab/aboBoNT-A) vs €1,793 (rehab). Over a period of 2 years rehab/aboBoNT-A outperforms rehab in terms of quality-adjusted life years gained (1.620 vs 1.150). The incremental cost-utility ratio was €12,341 (Italian National Health Service viewpoint) and €23,601 (societal viewpoint). Sensitivity analyses confirmed the robustness of the baseline results. CONCLUSION: Despite some limitations, the higher number of quality-adjusted life years gained vs rehab and the high probability of reaching a cost-utility ratio lower than the Italian informal acceptability range (€25,000-40,000) make rehab/aboBoNT-A a cost-effective healthcare programme for treating patients with post-stroke spasticity in Italy.

Healthcare costs of the SATisfaction and adherence to COPD treatment (SAT) study follow-up.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by recurring exacerbations. We estimated the costs of healthcare resources for COPD management funded by the Italian National Healthcare Service (INHS) for one year. METHODS: We examined the demographic, clinical, and economic variables at enrolment and follow-up visits (at 6 and 12 months) of COPD patients participating in the SAT study and referred to 20 Italian pulmonary centres with different institutional characteristics. Costs were expressed in Euro (€) 2018. A random effects log-linear panel regression model was performed to predict the average cost per patient. RESULTS: Most of the centres were public institutions (90%; public university hospital: 30%). The total average cost of COPD was €2647.38/patient and ICS/LABA/LAMA therapy contributed the most (€1541.45). The average cost was €6206.19/patient for severe COPD (+139.67% vs the cost/patient with mild or moderate COPD). The regression model showed that, others things being equal, increases in the predicted average logged cost per patient were due to liquid oxygen therapy (+468.31%), three COPD exacerbations during the follow-up (+254.54%), and ICS/LABA or ICS/LABA/LAMA associated therapy (+59.26%). Moreover, a 1.19% increment was observed for each additional score of the CAT questionnaire. Conversely, a 36.52% reduction in the predicted average logged cost was reported for hospitals managed by local healthcare authorities. CONCLUSIONS: The health econometric approach is innovative in the management of COPD patients in Italy. The results of the random effects log-linear panel data regression model may help clinicians estimate INHS costs when managing COPD patients. Clinicaltrials.gov ID# NCT02689492.

Consensus conference on the management of tumor lysis syndrome.

Tumor lysis syndrome is a potentially life threatening complication of massive cellular lysis in cancers. Identification of high-risk patients and early recognition of the syndrome is crucial in the institution of appropriate treatments. Drugs that act on the metabolic pathway of uric acid to allantoin, like allopurinol or rasburicase, are effective for prophylaxis and treatment of tumor lysis syndrome. Sound recommendations should regulate diagnosis and drug application in the clinical setting. The current article reports the recommendations on the management of tumor lysis syndrome that were issued during a Consensus Conference project, and which were endorsed by the Italian Society of Hematology (SIE), the Italian Association of Pediatric Oncologists (AIEOP) and the Italian Society of Medical Oncology (AIOM). Current concepts on the pathophysiology, clinical features, and therapy of tumor lysis syndrome were evaluated by a Panel of 8 experts. A consensus was then developed for statements regarding key questions on tumor lysis syndrome management selected according to the criterion of relevance by group discussion. Hydration and rasburicase should be administered to adult cancer patients who are candidates for tumor-specific therapy and who carry a high risk of tumor lysis syndrome. Cancer patients with a low-risk of tumor lysis syndrome should instead receive hydration along with oral allopurinol. Hydration and rasburicase should also be administered to patients with clinical tumor lysis syndrome and to adults and high-risk children who develop laboratory tumor lysis syndrome. In conclusion, the Panel recommended rasburicase for tumor lysis syndrome prophylaxis in selected patients based on the drug efficacy profile. Methodologically rigorous studies are needed to clarify its cost-effectiveness profile.