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 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.

An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) + gemcitabine vs gemcitabine alone for metastatic pancreatic cancer patients: the APICE study.

BACKGROUND: the APICE study evaluates the cost-effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel - Nab-P) + gemcitabine (G) vs G alone in metastatic pancreatic cancer (MPC) from the Italian National Health Service (INHS) standpoint. RESEARCH DESIGN AND METHODS: A 4-year, 4 health states (progression-free; progressed; end of life; death) Markov model based on the MPACT trial was developed to estimate costs (Euro [€], 2017 values), and quality-adjusted life years (QALYs). Patients were assumed to receive intravenously Nab-P 125 mg/m2 + G 1000 mg/m2 on days 1, 8, and 15 every 4 weeks or G alone 1000 mg/m2 weekly for 7 out of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles) until progression. One-way and probabilistic sensitivity analyses explored the uncertainty surrounding the baseline incremental cost-utility ratio (ICUR). RESULTS: Nab-P + G totals 0.154 incremental QALYs and €7082.68 incremental costs vs G alone. ICUR (€46,021.58) is lower than the informal threshold value of €87,330 adopted by the Italian Medicines Agency during 2010-2013 for reimbursing oncological drugs. Sensitivity analyses confirmed the robustness of the baseline findings. CONCLUSIONS: Nab-P + G in MPC patients can be considered cost-effective for the INHS.

Cost of illness in patients with multiple myeloma in Italy: the CoMiM study.

AIMS AND BACKGROUND: Multiple myeloma is the second most common hematological cancer. Although it accounts for only a relatively small percentage of all cancer types, the costs associated with managing multiple myeloma are considerable. Available studies are mainly focused on health care costs. The Costo del Mieloma Multiplo (Cost of MM, CoMiM) study investigated the cost of illness of multiple myeloma in Italy during one year of disease management. METHODS: CoMiM is a retrospective, prevalence-based, multi-center, cross-sectional study based on a stratified sample of patients seen during normal clinical practice (asymptomatic; symptomatic on drugs; symptomatic receiving autologous stem cell transplantation; plateau/remission). Demographics, clinical history, health care and non-health care resource consumption data were collected. Costs were evaluated from the societal viewpoint and expressed in Euro 2008. RESULTS: Data on 236 patients were analyzed (39 asymptomatic, 17%; 29 symptomatic receiving autologous stem-cell transplantation, 12%; 105 symptomatic receiving drugs, 44%; 63 plateau/remission, 27%). The total cost of illness reached € 19,267.1 ± 25,078.6 (asymptomatic, € 959.3 ± 1091.6; symptomatic receiving drugs, € 21,707.8 ± 21,785.3; symptomatic receiving autologous stem-cell transplantation, € 59,243.7 ± 24,214.0; plateau/remission, € 8130.7 ± 15,092.5). The main cost drivers of total cost of illness were drugs and hospital admissions (46.1% and 29.4%, respectively). Antineoplastics and immunomodulators drove the cost of drugs (21.6% and 21.1% of the total cost of illness). Cost of antineoplastics was led by bortezomib (97.4%), whereas the cost driver for immunomodulators was lenalidomide (99.4%). Cost of hospitalization funded by the Italian National Health Service was strongly influenced by transplantation (94.6%), whereas chemotherapy and skeletal fractures did not exceed 1% and 2%, respectively. CONCLUSIONS: Despite some limitations, the CoMiM study provides Italian health care decision-makers with an insight into the stratified cost of illness of multiple myeloma patients.

An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) versus conventional paclitaxel for metastatic breast cancer patients: the COSTANza study.

PURPOSE: Paclitaxel albumin (nab-paclitaxel) is a nanoparticle albumin-bound paclitaxel formulation aimed at increasing therapeutic index in metastatic breast cancer. When compared to conventional paclitaxel, nab-paclitaxel has a reported longer time to progression, higher response, lower incidence of neutropenia, no need for premedication, shorter time of administration, and in pretreated metastatic breast cancer patients, extended overall survival. This study investigates the cost-effectiveness of nab-paclitaxel versus conventional paclitaxel for pretreated metastatic breast cancer patients in Italy. MATERIALS AND METHODS: A Markov model with progression-free, progressed, and dead states was developed to estimate costs, outcomes, and quality adjusted life years over 5 years from the Italian National Health Service viewpoint. Patients were assumed to receive nab-paclitaxel 260 mg/m(2) three times weekly or conventional paclitaxel 175 mg/m(2) three times weekly. Data on health care resource consumption was collected from a convenience sample of five Italian centers. Resources were valued at Euro (€) 2011. Published utility weights were applied to health states to estimate the impact of response, disease progression, and adverse events on quality adjusted life years. Three sensitivity analyses tested the robustness of the base case incremental cost-effectiveness ratio (ICER). RESULTS AND CONCLUSION: Compared to conventional paclitaxel, nab-paclitaxel gains an extra 0.165 quality adjusted life years (0.265 life years saved) and incurs additional costs of €2506 per patient treated. This translates to an ICER of €15,189 (95% confidence interval: €11,891-€28,415). One-way sensitivity analysis underscores that ICER for nab-paclitaxel remains stable despite varying taxanes cost. Threshold analysis shows that ICER for nab-paclitaxel exceeds €40,000 only if cost per mg of conventional paclitaxel is set to zero. Probabilistic sensitivity analysis highlights that nab-paclitaxel has a 0.99 probability to be cost-effective for a threshold value of €40,000 and is the optimal alternative from a threshold value of €16,316 onwards. Based on these findings, nab-paclitaxel can be considered highly cost-effective when compared to the acceptability range for ICER proposed by the Italian Health Economics Association (€25,000-€40,000).

[Economic evaluation of posaconazole in prophylaxis of invasive fungal infections in Italian neutropenic patients with acute myeloid leukaemia or myelodysplastic syndrome]. / Valutazione economica di posaconazolo in prevenzione di infezioni fungine invasive nel paziente immunocompromesso affetto da leucemia mieloblastica acuta o da sindrome mielodisplasica in Italia.

The objective of this study was to assess the costs and effectiveness (avoided invasive fungal infections - IFIs; overall mortality) of prophylaxis with posaconazole 200 mg per os TID and standard azoles (fluconazole 400 mg per os OD, itraconazole 200 mg per os BID) in neutropenic patients with acute myelogenous leukaemia or myelodysplastic syndromes. A 100-day cost-effectiveness model was developed following the Italian hospital perspective. The probability of IFIs, death from IFIs, and death from other causes was obtained from the literature. Health care sector resources (type, volume, unit cost) are given in Euros and refer to 2009. The robustness of the cost-effectiveness model was tested via one-way and probabilistic sensitivity analyses. Total costs for posaconazole (standard azoles) was estimated at Euros 3365.26 (Euros 2339.96). Posaconazole is consistently more effective than standard azoles. The incremental cost-effectiveness ratio for avoided IFI (avoided overall mortality) with posaconazole is Euros 15,850.51 (Euros 18,038.43). Sensitivity analyses confirmed the robustness of such findings. In conclusion, posaconazole as a prophylaxis in neutropenic patients with AML or MDS who are at risk of IFI is good value for money for Italian hospitals.

Economic evaluation of treating clinically isolated syndrome and subsequent multiple sclerosis with interferon beta-1b.

New therapeutic options have modified the natural history and health care costs of multiple sclerosis (MS). An epidemiological 25 years-long model-based cost-utility analysis was performed following the Italian National Health Service (INHS) and societal perspectives to compare costs and quality-adjusted life years of treatment with Interferon beta-1b (IFNB-1b) from diagnosis of clinically isolated syndrome (CIS) versus treating at subsequent conversion to clinically definite MS (CDMS). Among patients treated (untreated) with IFNB-1b from CIS diagnosis, 40,420 (43,700) converted to CDMS after 25 years; the estimated cumulative probability of converting to CDMS during the first 3 years was 72.90% (84.94%) (P < 0.0001). Early treatment with IFNB-1b is highly cost-effective for the INHS (incremental cost-effectiveness ratio: Euros 2,574.94) and dominant from the societal viewpoint. Sensitivity analyses confirmed the base case findings. Early treatment with IFNB-1b delays conversion to CDMS in CIS patients and might be a "good value for money" health care programme.

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.

Economic evaluation of different hormonal therapies for prostate cancer. Final results from the Quality of Life Antiandrogen Blockade Italian Observational Study (QuABIOS).

OBJECTIVE: The paper compares costs and Quality-Adjusted Life Years (QALYs) of different hormonal therapies (HTs) administered to 275 out of 471 patients with prostate cancer (PC) enrolled in the Quality of Life Antiandrogen Blockade Italian Observational Study (QuABIOS), who did not change HT during the study period. METHODS: QALYs and costs related to monoHT witk cyproterone acetate (CYP) (42 patients); bicalutamide (BIC) (41 patients); LHRH-a (96 patients) and complete androgenic blockade (CAB) with: CYP (CYP CAB) (50 patients); BIC (BIC CAB) (46 patients) were compared via a cost-utility analysis (CUA) adopting the Italian National Healthcare Service (INHS) viewpoint. RESULTS: As no statistical significant difference among the mean QALYs gained with the different HTs was detected (p = 0.116), CUA was replaced by a cost minimization analysis (CMA). However, the lowest and the highest mean QALYs gained per patient were registered for BIC CAB (0.59; 95% CI: 0.50; 0.68) and for for CYP (0.75; 95% CI: 0.68; 0.82), respectively. CYP was the least costly HT, reaching the lowest and the highest savings when compared to LHRH-a (-Euros 974.99; 95% CI: -Euros 1066.86; -Euros 883.12; p<0.0001) and to monoHT with BIC (-Euros 5887.81; 95% CI: -Euros 6143.99; -Euros 5631.64; p<0.0001). A nonparametric bootstrap sensitivity analysis confirmed the robustness of the base case CMA. CONCLUSION: CYP is an interesting option for curbing the INHS drug expenditure for PC patients, with a trend towards increasing the mean number of QALYs gained.

[Managing patients with prostate cancer in Italy during the first year after diagnosis. A cost description based on a sample of 8 urological wards]. / Managing patients with prostate cancer in Italy during the first year after diagnosis. A cost description based on a sample of 8 urological wards.

OBJECTIVE: The aim of the paper is to report of an empirical retrospective study (1994-1999) on the cost of managing patient with prostate cancer (PC) during the first year after diagnosis in Italy. MATERIAL AND METHODS: In January 2000, a questionnaire on qualitative, quantitative and economic data concerning the clinical path expected for patients with PC (diagnosis; staging; follow-up; drug; surgery; chemotherapy and radiotherapy) was sent to 14 Italian urological wards (UWs), 5 school of medicine-based (Northern Italy: 2; Central Italy: 1; Southern Italy: 2), 4 self-governing hospital-based (Northern Italy: 1; Southern Italy: 3), 5 Health Authorities hospital-based (Northern Italy: 2; Central Italy: 2; Southern Italy: 1). UWs were expected to contribute to analysis with 15 patients' records per year each, for a total amount of 1.260 filled questionnaires. Only medical costs related to patient management have been considered; hospitals and Health Authorities overheads were not taken into account. A cost description was performed considering the hospital viewpoint. RESULTS: We received 416 out of 1.260 expected questionnaires (redemption rate: 33%) from 8 out of 14 UWs: 2 school of medicine-based (Central Italy: 1; Southern Italy: 1); 2 self-governing hospital-based (Southern Italy: 2); 4 Health Authorities hospital-based (Northern Italy: 1; Central Italy: 3). Only 411 out of 416 questionnaires were included in data analysis. Patients' average age at the time of diagnosis was 74.1 years (range: 68.6-76.7). A moderate percentage of neoplasms in patients' relatives was reported (17.8%; 5.6% for PC). The average cost per patient with CP during the first year after diagnosis was Euro 6,575.31 (range: Euro 5,035.65-Euro 12,367.69). The cost-driver was drug therapy (43.07%), followed by surgery (26.41%), diagnosis (12.39%), staging (8.58%); follow-up (8.25%) and radiotherapy (1.30%); no data on chemotherapy was reported. Diagnosis, staging and follow-up tests and procedures were performed mainly in outpatient setting (81.84% 53.30% and 94.72%, respectively) and requested by hospital urologists (70.26%; 52.88% and 67.95%, respectively). Total PSA was the most frequent test for diagnosis (503 out of 2,047 procedures) and follow-up (782 out of 3,351 procedures), as well as bone scan was for staging (337 out of 1,023 procedures). As far as drug therapy is concerned, LHRH-analogue was the most prescribed drug (227 patients). Surgery (lymphoadenectomy: 9; orchidectomy: 20; urinary outlet dysobstruction: 51; prostatectomy: 104) was performed in 179 patients; 5 out of 179 patients underwent more than one surgical intervention. Radiotherapy (338 sessions) was undertaken in 15 out of 411 patients. CONCLUSIONS: Cost of managing patient with PC during the first year after diagnosis in Italy could be reduced by increasing outpatient procedures and decreasing post-surgery hospital stay. Our research may hopefully foster further empirical studies on the health economics of PC in our country.

[The economics of managing patients with prostate cancer]. / The economics of managing patients with prostate cancer.

OBJECTIVE: The aim of the paper is to report on the economics of managing patients with prostate cancer (PC). MATERIAL AND METHODS: After a thorough research on MEDLINE, 15 recent articles (1994-2000) concerning the economics of PC have been selected. Costs taken from articles were supplemented with accounting data provided by Research and Teaching Hospital San Raffaele, Milan. Only medical costs have been considered. RESULTS: In Western countries, PC is becoming one of the most frequent neoplasms among males, with a 20% life-time probability of occurrence. In the near future, the global burden of illness related to PC is expected to grow consistently with the increasing number of 50-aged men. The average survival of PC patients is generally increased, probably due to the improvement of diagnostic tests, instruments and programmes. When targeted to selected classes of men, screening for early diagnosis of PC seems to be cost-effective when compared to "watchful waiting", since cost per Quality-Adjusted Life Year (QALY) gained ranges between US$ 12,502 and US$ 27,025. Healthcare programmes are deemed cost-effective if cost per life year (or per QALY) gained is lower than US$ 50,000. In USA, the total cost for treating PC patients has reached US$ 1,720 billion per year; cost for radical prostatectomy approaches US$ 19,000. The average Italian cost for prostatectomy (Euro 4,000) is hardly covered by Regional DRG reimbursement (Euro 3,600 in Lombardy). When brachytherapy is considered, the gap between cost (Euro 4,806) and DRG tariff (Euro 3,500 in Lombardy) becomes even wider; this difference is mainly due to the high cost of I-125 needles (Euro 55,77 each). In 1997, USA drug expenditure for PC has approached 761 million US$: LH-RH analogues and antiandrogens account for a relevant share of this amount. However, LH-RH analogues can be the only treatment option for a metastatic PC patient who refuses orchiectomy. CONCLUSIONS: In managing PC, urologists are increasingly faced with healthcare budget constraints. Cost for surgery may be decreased by reducing either operating time or length of hospital stay. Drug expenditure may be cut by choosing the cheapest of drugs with the same effectiveness.