Cost-utility analysis of palivizumab in Italy: results from a simulation model in the prophylaxis of respiratory syncytial virus infection (RSV) among high-risk preterm infants

Abstract Introduction The aim of this study was to assess the cost-utility of palivizumab versus no prophylaxis in the prevention of respiratory syncytial virus infection among high-risk preterm infants. Methods We used and adapted a pre-existent model in which two cohorts of patients received palivizumab or no prophylaxis. The patients were followed for their expected lifetimes. The economic evaluation was conducted from the perspective of the Italian National Health Service. We considered Life-Years Gained (LYGs), Quality-Adjusted Life-Years (QALYs) and direct medical costs (pharmacological treatment, hospitalization, recurrences for wheezing, etc.). LYGs and QALYs were based on the results of a double blind cohort study with prospective follow-up and direct medical costs were based on Italian treatment patterns. Benefits and costs were discounted at 3%. Costs were assessed in 2007 Euros. Sensitivity and threshold analysis on key clinical and economic parameters were performed. Result For the two cohorts, the expected life-years (per patient) with palivizumab versus no prophylaxis were 29.842 and 29.754 years, respectively. Quality-adjusted life years (per patient) with palivizumab were 29.202, and for no prophylaxis were 29.043. The expected cost (per patient) was € 6,244.20 with palivizumab and € 4,867.70 with no prophylaxis. We calculated for palivizumab versus no prophylaxis the incremental cost per LYG and per QALY gained. It was € 15,568.65 and € 8,676.74, respectively. Conclusion This study suggests that, compared with no prophylaxis, palivizumab is cost-effective in the prevention of respiratory syncytial virus infection among high risk preterm infants.</p

Analysis of the cost-effectiveness of surfactant treatment (Curosurf®) in respiratory distress syndrome therapy in preterm infants: early treatment compared to late treatment

BACKGROUND: The best criteria for surfactant treatment in the perinatal period are unknown and this makes it of interest to consider the possible economic implications of lessening the use of more restrictive criteria. OBJECTIVE: The objective of this study is the evaluation of the costs of respiratory care for preterm infants with Respiratory Distress Syndrome (RDS) treated with "early rescue" surfactant compared to a "late rescue" strategy. METHODS: The study was carried out applying the costs of materials used, of staff and pharmacological therapy calculated in the Neonatal Intensive Care Unit (NICU) of an Italian hospital to the Verder et al. study (Pediatrics 1999) clinical data. RESULTS: The cost for patients treated with early strategy was slightly lower than for patients treated with late strategy (Euro 4,901.70 vs. Euro 4,960.07). The cost of treatment with surfactant was greater in the early group (Euro 458.49 vs. Euro 311.74), but this was compensated by the greater cost of treatment with Mechanical Ventilation (MV) in the late group (respectively Euro 108.85 vs. Euro 259.25). CONCLUSIONS: The cost-effectiveness analysis performed in this study shows how early treatment with surfactant in preterm infants with RDS, as well as being clinically more effective, is associated with a slightly lower cost

Cost-Consequence Analysis of Three Different Diagnostic Strategies in the First- and Second-Line Treatment of Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

BACKGROUND: Unlike the tissue one, liquid biopsy is a less invasive diagnostic method for the assessment of possible mutations of the tumor, based on the analysis of circulating free DNA (cfDNA) present in the plasma component of the blood. Because blood samples are easily obtainable, plasma biopsy is a non-invasive method, supplementing the more traditional biopsy techniques.AIM: A cost-consequence analysis was conducted to compare the adoption of three different diagnostic strategies in the first- and second-line treatment of locally advanced or metastatic NSCLC: i) tissue strategy (only tissue biopsy for first and second line), ii) combined strategy (first line: tissue biopsy. If unknown, liquid biopsy; second line: liquid biopsy. If negative, tissue biopsy) and iii) potential strategy (first line: tissue biopsy. If unknown or tissue ineligible, liquid biopsy; secondline: liquid biopsy. If negative, tissue biopsy).METHODS: A decision-analytic model was developed considering the Italian NHS’s perspective. We only evaluated direct medical costs (tissue biopsy, management of complications associated with tissue and liquid biopsies) borne by the NHS. The CCA was conducted over a time horizon of 1 year, assuming that for each patient with mNSCLC the diagnosticpathway (first- and second-line treatment) ended within such period. Key variables were tested in the sensitivity analysis.RESULTS: Considering both the first and the second line of treatment, the potential strategy constitutes the cost-effective alternative, characterized by an average cost per correctly identified case (€ 685) lower than that estimated for the combined strategy (€ 732) or for the tissue strategy (€ 1,004). The potential strategy remains cost-effective, also considering the results referred to the first- or second-line treatment only.CONCLUSION: The choice of a correct diagnostic strategy is crucial in order to optimize cancer therapies in the first- and second-line treatment of locally advanced or metastasized NSCLC. The addition to the diagnostic pathway of the liquid biopsy would correctly identify a greater number of cases, supporting the prescription of the best oncological therapy

The value of obinutuzumab for untreated advanced Follicular Lymphoma: an assessment based on Multicriteria Decision Analysis (MCDA)

Introduction: Multicriteria Decision Analysis (MCDA) provides a framework that enhances transparency and repeatability of decisions taken on a multicriteria basis. Objective: This analysis aims at assessing obinutuzumab compared to rituximab used as a first-line treatment for Follicular Lymphoma (FL) in the Italian health care system, using an MCDA approach. Materials and Methods: We used the EVIDEM V10 MCDA framework and a Delphi approach to scrutinize the views of a panel of physicians, payers and patients on value domains and their application to our research target. Results: All stakeholders attached medium-high scores to FL severity (patients at higher risk of relapsing), unmet needs, obinutuzumab clinical benefit and evidence quality, and lower scores to organizational impact and, except for payers, to costs. The comparative analysis highlighted positive scores for the domains "incremental efficacy" (2.6: range −5/+5) and "incremental patient benefit" (1.5: range −5/+5) of obinutuzumab compared to rituximab. A slight increase of severe adverse events (≥3) for obinutuzumab was estimated by the panellists. Obinutuzumab compared to rituximab received a neutral evaluation for costs and for organizational impact. Conclusion: This study reveals that MCDA could be a useful framework for evaluating a drug and it can be used to elicit the views of different stakeholder groups (as patients). The key criteria driving the value of obinutuzuma

Economic implications in inflammatory bowel disease: results from a retrospective analysis in an Italian Centre

BACKGROUND: Inflammatory bowel disease (IBD) represents a group of chronic conditions characterized by elevated costs. Over the last years, also a considerable healthcare burden associated with IBD has emerged, due to an increasing use of biological drugs and hospitalization costs. Despite the creation of local or regional databases, data regarding healthcare expenditure are lacking in Italy.AIM: To evaluate the treatment cost (biological drugs and hospitalizations) for patients with ulcerative colitis (UC) or Crohn’s disease (CD) treated with biological drugs.METHODS: Disease severity was evaluated by clinical scores (partial Mayo score and Harvey Bradshaw Index). We analyzed retrospectively patients treated with biologics referred to our IBD Unit between May 2015-April 2016 who underwent at least six months of follow-up (last visit October 2016). We calculated a mean cost per month of treatment for each patient. We also investigated the presence of any correlation between the monthly cost of treatment and demographic or clinical variables.RESULTS: We enrolled 142 patients (52 UC, mean age 44.3 years, male 40.4%; 90 CD, mean age 38.8 years, male 56.7%). About half of CD patients (48.9%) underwent previous intestinal surgery. The disease severity was higher in UC group vs CD group. In UC group infliximab was the most prescribed biologic (51.9%), followed by golimumab (26.9%) and adalimumab (21.2%). While CD patients were treated with adalimumab in 54.4% and infliximab in 45.6%. The mean monthly cost of treatment was € 1,235.41 ± 358.38 for UC and € 1,148.92 ± 337.36 for CD (p = 0.16). In both groups expenditure due to biologics amounts for more than 80%. We found a correlation between costs and disease activity (UC: p < 0.01; CD: p < 0.01).CONCLUSION: The main cost is due to biological drugs, but patients enrolled were the most severe in comparison to the whole IBD population under conventional therapy. As no cost differences were found between biologic drugs and the way of administration (intravenous or subcutaneous), the therapeutic choice should be driven by clinical reasons and not only economic ones

Clinical Impact of two Different Diagnostic Strategies in the First- and Second-Line Treatment of Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

BACKGROUND: A histopathological and mutational diagnosis has become a priority in the correct choice of the most appropriate cancer therapy for NSCLC. In the absence of a molecular analysis, the therapeutic choice will be directed towards platinum-based chemotherapy, thus preventing, in the presence of a specific mutation, the benefits deriving from the administration of a target therapies (TT).AIM: the present analysis was carried out with the aim of estimating the clinical impact, expressed in terms of progression free survival (PFS), associated with the use of the combined strategy (tissue biopsy and liquid biopsy) or the tissue strategy in the EGFR+ mNSCLC population.METHODS: A pre-existing cost-consequence model was adapted to estimate the annual number of mNSCLC patients with or without the EGFR mutation in order to decide the oncological treatment to be administered in first (1L) or second line (2L). In 1L, against the presence of the EGFR mutation, the administration of a Tyrosine Kinase Inhibitor (TKI), such as osimertinib, gefitinib, erlotinib or afatinib, was considered; in the absence of the EGFR mutation, the administration ofstandard platinum-based chemotherapy was instead considered. With reference to 2L, in the presence of the EGFR T790M mutation, only osimertinib was considered. In the absence of the EGFR T790M mutation, the administration of the standard platinum-based chemotherapy was also considered. The PFS data associated with each of the drugs considered were extrapolated from the respective clinical studies. Key variables were tested in the sensitivity analysis.RESULTS: The adoption of the combined strategy (tissue biopsy and liquid biopsy), by virtue of a greater number of patients treated with TKIs, would make it possible to increase the average PFS in the range of 1.1-3,7 months in the 1L and by 1.4 months in the 2L.CONCLUSION: These results show how the adoption of a correct diagnostic strategy is critical in order to optimize the choice of the therapeutic path in the 1L and 2L of mNSCLC. The addition of the liquid biopsy to the classic diagnostic path (tissue biopsy) would in fact allow to obtain an increase in therapeutic efficacy (average PFS)

Valutazione economica dei costi associati al trattamento di pazienti in ossigenoterapia a lungo termine, con o senza monitoraggio telemetrico domiciliare

Long term oxygen treatment (LTOT) represents an helpful, even though costly, therapeutic strategy for managing severe chronic respiratory diseases at home. The aim of the present study was to assess the economic impact of adding the home telemetric monitoring of some vital signs to the traditional domiciliary LTOT in this kind of patients. Two samples of severe chronic respiratory patients (COPD patients in 89% of cases, managed at home without, n=20, and with, n= 61, telemetric home monitoring) were compared for a 24-month period, and the corresponding outcomes measured. In the tele-monitored group of subjects, both the mean number and the mean duration of hospitalisations dropped along the two-year study, together with the n. exacerbations/ patient/year. The mean annual cost for the tele-monitored group of patients was lower by 28% in the first year, and by 33% in the second year of the study. The home tele-LTOT management of patients with severe chronic respiratory disease, mostly COPD, allows a better clinical control of the disease, with a corresponding 50% reduction of exacerbations leading to hospitalisation. Finally, the home tele-LTOT contributes substantially in minimizing the economic impact of these severe chronic respiratory diseases

Diagnostic work-up and management of young patients with ulcer-like dyspepsia: A cost-minimisation study

Objective: We initiated a cost-minimisation modelling study to compare the costs of strategies based on initial endoscopy or initial non-invasive tests for the detection of Helicobacter (C13 UBT or serology) from the perspective of the Italian National Health Service. The secondary outcomes were the number of patients undergoing unnecessary Helicobacter pylori (HP) eradication treatment and the number of endoscopic examinations spared.Methods: The study was based on a decision analysis model referring to patients aged less than 45 years with ulcer-like dyspepsia and no alarming symptoms. The probabilities entered in the model were weighted means from published studies, and the costs were derived from the Italian NHS reimbursement schedule. Sensitivity analyses were conducted over a wide range of probability and cost estimates in order to test the robustness of the model.Results: Non-invasive tests (such as the preliminary work-up of patients with ulcer-like dyspepsia aged less than 45 years) were cheaper ..

Pharmacokinetics of ketamine and norketamine following intramuscular administration combined with dexmedetomidine in tigers (Panthera tigris)

In zoo practice, for physical examination or medical procedure in captive tigers, chemical immobilization is needed and ketamine (KET) in association with sedatives is an option frequently used (Clark-Price et al., 2015). Aims of the study is the assessment of the pharmacokinetics of KET and its main metabolite, norketamine (NORKET), after its intramuscular administration in combination with dexmedetomidine in tigers.Nineteen adult captive tigers, from different zoos, were scheduled for periodic physical examination or diagnostic procedures at the Milan University facilities. All animals were administered with a combination of KET at 2 mg/kg and dexmedetomidine at 10 µg/kg, given intramuscularly through blowpipe darts. If necessary, tigers where re-administered with variable doses of KET and dexmedetomidine or other drugs. When animals were sufficiently sedated, blood samples were collected every 5-10 min for the time tigers were safely approachable. Nine animals were assigned to standard protocol group (KET 2 mg/kg and dexmedetomidine 10 µg/kg) and ten animals to non-standard protocol group (tigers administered with different doses of KET, 2 – 2.5 mg/kg, and dexmedetomidine 10 – 30 µg/kg or with any other necessary drug, such as titrate-to-effect propofol and isoflurane, respectively for anaesthesia induction and maintenance). Ketamine and NORKET were extracted from plasma according to a validated HPLC-UV method (Zonca et al., 2012). For pharmacokinetic assessment, KET and NORKET concentrations were analysed with a noncompartmental approach (Phoenix® 7.0, Pharsight). Differences in the pharmacokinetic parameters between groups were statistically analysed (SPSS 25.0, SPSS Inc.).This is the first study that evaluates the pharmacokinetics of KET and NORKET in tigers. Due to the harmful attitude of these animals, samples collection was limited to the period of sedation, a short time for a complete pharmacokinetic evaluation. Nevertheless, we observed a favorable kinetic profile of KET and NORKET and, from a clinical point of view, all animals showed a good recovery, no adverse effects and a good level of sedation.     Standard Protocol              (mean ± s.d.)Non-Standard protocol             (mean ± s.d.)     KetamineHL_Lambda_zmin77.62 ± 54.5076.14 ± 67.32 Tmaxmin27.78 ± 7.9049.70 ± 29.64 Cmaxug/mL0.63 ± 0.170.67 ± 0.19 AUClastmin*ug/mL23.84 ±6.40*35.97 ± 12.84* AUMClastmin*min*ug/mL802.24 ± 331.03*2054.97 ± 1018.88* MRTlastmin32.88 ± 5.71*54.38 ± 19.71*     NorketamineTmaxmin51.89 ± 8.95*77.10 ± 24.41* Cmaxug/mL0.24 ± 0.070.23 ± 0.09 AUClastmin*ug/mL7.30 ± 3.9811.07 ± 5.46 AUMClastmin*min*ug/mL291.94 ± 227.01*701.87 ± 424.80* MRTlastmin36.95 ± 7.32*58.65 ± 19.58*HL_Lambda_z = Elimination Half-Life; Tmax = Time to Maximum concentration; Cmax = Maximum Concentration; AUClast = Area Under the Curve to the last concentration; AUMClast = Area under the first Moment Curve to the last concentration ;MRTlast = Mean Residence Time to the last concentration  Tab.1: Pharmacokinetic parameters of ketamine and norketamine in nineteen adult captive tigers after intramuscular administration of 2 mg/kg of ketamine, with or without variation from the standard protocol, in combination with dexmedetomidine (with * are indicated results with p &lt; 0.05)