Economic impact of a more extensive use of FENO testing on the Italian population with asthma.

BACKGROUND: Asthma is a common chronic inflammatory airway affecting over 260 million people worldwide, and characterized, in the large majority of cases, by the so-called "type 2 inflammation". Fractional exhaled nitric oxide (FENO) testing is noninvasive point-of-care tool to assess type 2 inflammation and therefore improve asthma management. It has been suggested to determine eligibility for a specific biologic therapy and predict likelihood to respond. The aim of this study was to estimate the overall economic impact of an extensive use of FENO testing on the Italian population with asthma, including extra costs of testing and savings generated by more appropriate prescriptions, increased adherence and lower frequency of exacerbations. METHODS: A cost of illness analysis was firstly performed to estimate the yearly economic burden from the National Healthcare Service (NHS) perspective in Italy of the management of asthmatic patients with standard of care (SOC) according to the application of GINA (Global Initiative for Asthma) guidelines; then, we evaluated the changes in the economic burden in patient management by introducing FENO testing into clinical practice. The cost items considered were: visits/exams, exacerbations, drugs, management of adverse events caused by short-term oral corticosteroids use. Efficacy of FeNO test and SOC is based on literature evidence. Costs refer to published data or Diagnosis Related Group/outpatient tariffs. RESULTS: Considering one asthma visit every 6 months, the total yearly cost for the management of patients with asthma in Italy is 1,599,217,876€ (409.07€ per patient), while for FENO testing strategy this figure is 1,395,029,747€ (356.84€ per patient). An increased utilization rate of FENO testing from 50 to 100% of patients may lead to savings for the NHS from about 102 to 204 million € compared to SOC. CONCLUSIONS: Our study showed that FeNO testing strategy may improve the management of asthmatic patients leading to significant savings for the NHS.

Broadening the Concept of Value: A Scoping Review on the Option Value of Medical Technologies.

OBJECTIVES: A recent debate in health economics and outcomes research community identified option value as one of the elements warranting consideration in the assessment of medical technologies. To conduct a scoping review of contributions on option value in the healthcare sector and identify relevant conceptual aspects and methods used to incorporate it in standard economic evaluations. METHODS: A systematic search was conducted up to July 2020 to identify contributions from electronic bibliographic database and gray literature. Data on the proposed definitions of option value, theoretical implications of its use in economic evaluations, and methods used to estimate it were extracted and analyzed. RESULTS: We found 57 eligible studies. Three different definitions emerged: insurance value, real option value, and option value of survival. Focusing on the latter (24 studies), we analyzed in depth 8 empirical applications across 7 therapeutic areas. The most relevant methodological challenges were on the perspective used in economic evaluations and how to robustly manage forecasting uncertainty, update cost-effectiveness thresholds, and avoid double-counting issues. For empirical studies assessing the total value of the technology, including option value, estimates ranged from +7% to +469% of its conventional value. CONCLUSIONS: This review synthesizes theoretical and empirical aspects on option value of healthcare technologies and proposes a terminology to distinguish 3 different concepts identified. Future work should focus primarily on agreeing on whether option value should be included in economic evaluations and, if so, on developing and validating reliable methods for its ex-ante estimation.

Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis.

BACKGROUND: Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line treatments, or both, based on chemotherapy and on hormone therapy have been scarcely investigated in head-to-head randomised controlled trials, we aimed to compare these two different approaches. METHODS: We did a systematic review and network meta-analysis with a systematic literature search on PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, and online archives of the most relevant international oncology conferences. We included all phase 2 and 3 randomised controlled trials investigating chemotherapy with or without targeted therapies and hormone therapies with or without targeted therapies as first-line or second-line treatments, or both, in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, published between Jan 1, 2000, and Dec 31, 2017. Additional recently published randomised controlled trials relevant to the topic were also subsequently added. No language restrictions were adopted for our search. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for progression-free survival (the primary outcome), and to compare odds ratios (ORs) for the proportion of patients achieving an overall response (the secondary outcome). All treatments were compared to anastrozole and to palbociclib plus letrozole. This study is registered in the Open Science Framework online public database, registration DOI 10.17605/OSF.IO/496VR. FINDINGS: We identified 2689 published results and 140 studies (comprising 50 029 patients) were included in the analysis. Palbociclib plus letrozole (HR 0·42; 95% credible interval [CrI] 0·25-0·70), ribociclib plus letrozole (0·43; 0·24-0·77), abemaciclib plus anastrozole or letrozole (0·42; 0·23-0·76), palbociclib plus fulvestrant (0·37; 0·23-0·59), ribociclib plus fulvestrant (0·48; 0·31-0·74), abemaciclib plus fulvestrant (0·44; 0·28-0·70), everolimus plus exemestane (0·42; 0·28-0·67), and, in patients with a PIK3CA mutation, alpelisib plus fulvestrant (0·39; 0·22-0·66), and several chemotherapy-based regimens, including anthracycline and taxane-containing regimens, were associated with better progression-free survival than was anastrozole alone. No chemotherapy or hormone therapy regimen was significantly better than palbociclib plus letrozole for progression-free survival. Paclitaxel plus bevacizumab was the only clinically relevant regimen that was significantly better than palbociclib plus letrozole in terms of the proportion of patients achieving an overall response (OR 8·95; 95% CrI 1·03-76·92). INTERPRETATION: In the first-line or second-line setting, CDK4/6 inhibitors plus hormone therapies are better than standard hormone therapies in terms of progression-free survival. Moreover, no chemotherapy regimen with or without targeted therapy is significantly better than CDK4/6 inhibitors plus hormone therapies in terms of progression-free survival. Our data support treatment guideline recommendations involving the new combinations of hormone therapies plus targeted therapies as first-line or second-line treatments, or in both settings, in women with hormone-receptor-positive, HER2-negative metastatic breast cancer. FUNDING: None.

Idiopathic Retroperitoneal Fibrosis: Long-term Risk and Predictors of Relapse.

RATIONALE & OBJECTIVE: Idiopathic retroperitoneal fibrosis (IRF) is a rare disorder of unknown cause. Medical therapy can induce remission, but disease relapses are common. This study sought to characterize long-term outcomes of IRF and the factors associated with disease recurrences. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Retrospective analysis of 50 patients with IRF prospectively followed up for 8.9 (IQR, 4.7-12.7) years at a tertiary-care referral center. EXPOSURES: Demographic, clinical, treatment, and laboratory parameters, including measures of autoimmunity. OUTCOME: Disease relapse. ANALYTICAL APPROACH: Proportional hazards analysis for the subdistribution of competing risks. RESULTS: 49 patients received medical treatment and 35 underwent interventional procedures. All patients experienced a clinical response (defined as regression of disease-related symptoms and hydronephrosis, and decrease in the maximal transverse diameter of the retroperitoneal mass on computed tomography of >50%), 44 of whom responded within 1 year. The remaining 6 responded over a median of 2.95 years after starting therapy. 40 patients were alive at last observation, 1 receiving maintenance dialysis and 15 with estimated glomerular filtration rate < 60mL/min/1.73m2. Patient survival at 5, 10, and 15 years was 95%, 84%, and 68%, respectively. 19 (38%) patients had at least 1 relapse (occurring a median of 5.19 years after starting therapy), defined as an increase in serum creatinine level of at least 30% or recurrence/development of hydronephrosis and ≥20% increase in the maximal transverse diameter of the retroperitoneal mass on computed tomography. Cumulative incidences of relapse at 5, 10, and 15 years were 21%, 41%, and 48%, respectively. Baseline antinuclear antibody positivity and male sex were associated with relapse (subdistribution hazard ratios [sHRs] of 5.35 [95% CI, 2.15-13.27] and 4.94 [95% CI, 1.32-18.57], respectively), while higher corticosteroid therapy dosage at 1 year (sHR for relapse per 1-mg/d greater dosage, 0.91 [95% CI, 0.84-0.98]) and treatment with prednisone alone or with tamoxifen (sHR for relapse of 0.25 [95% CI, 0.07-0.85] vs other therapies) were associated with lower rate of relapse. LIMITATIONS: Small sample size and variable approaches to therapy. CONCLUSIONS: IRF relapses were common and were experienced more frequently by male patients. Corticosteroids alone or with tamoxifen were associated with a lower rate of relapse. The strong association of antinuclear antibody positivity with relapse supports the hypothesis of an autoimmune pathogenesis of IRF.

Trans-arterial radioembolization for intermediate-advanced hepatocellular carcinoma: a budget impact analysis.

BACKGROUND: Trans-arterial radio-embolization (TARE) is an emerging treatment for the management of hepatocellular carcinoma (HCC). TARE may compete with systemic chemotherapy, sorafenib, in intermediate stage patients with prior chemoembolization failure or advanced patients with tumoral macrovascular invasion with no extra-hepatic spread and good liver function. We performed a budget impact analysis (BIA) evaluating the expected changes in the expenditure for the Italian Healthcare Service within scenarios of increased utilization of TARE in place of sorafenib over the next five years. METHODS: Starting from patient level data from three oncology centres in Italy, a Markov model was developed to project on a lifetime horizon survivals and costs associated to matched cohorts of intermediate-advanced HCC patients treated with TARE or sorafenib. The initial model has been integrated with epidemiological data to perform a BIA comparing the current scenario with 20 and 80% utilization rates for TARE and sorafenib, respectively, with increasing utilization rates of TARE of 30, 40 and 50% over the next 1, 3 and 5 years. RESULTS: Compared to the current scenario, progressively increasing utilization rates of TARE over sorafenib in the next 5 years is expected to save globally about 7 million Euros. CONCLUSIONS: Radioembolization can be considered a valuable treatment option for patients with intermediate-advanced HCC. These findings enrich the evidence about the economic sustainability of TARE in comparison to standard systemic chemotherapy within the context of a national healthcare service.

Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immune-mediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II-IV acute graft-versus-host disease (GVHD). METHODS: We conducted a multicentre, randomised, open-label, phase 3 trial in seven Italian centres comparing two different doses of ATLG (30 mg/kg vs 15 mg/kg, given intravenously over 3 days, from day -4 to -2) in children (aged 0-18 years) with haematological malignancies transplanted from an unrelated donor, selected using high-resolution typing for HLA-class I/II loci. All patients received a myeloablative regimen and cyclosporine-A plus short-term methotrexate as post-transplantation GVHD prophylaxis. Patients were randomly assigned (1:1) to either of the two groups and were stratified by the degree of HLA-compatibility with their donor, the source of haemopoietic stem cells used (bone marrow vs peripheral blood stem cells), and the disease risk category. The randomisation was open label; all investigators were aware of the treatment allocation. The primary endpoint of the study was 100-day cumulative incidence of grade II-IV acute GVHD. Statistical analyses were done according to the per-protocol principle. Other outcomes included cumulative incidence of chronic GVHD, non-relapse mortality, disease recurrence, and probability of overall survival and event-free survival. This study was registered with ClinicalTrials.gov, number NCT00934557. FINDINGS: Between Jan 15, 2008, and Sept 25, 2012, 89 patients were randomly assigned to the 30 mg/kg ATLG group and 91 to the 15 mg/kg ATLG group; 84 patients in the 30 mg/kg ATLG group and 88 in the 15 mg/kg ATLG group were included in the analysis. The median follow-up for the whole study population was 3·4 years (IQR 1·7-5·1). The 100-day cumulative incidence of grade II-IV acute GVHD was 36% (95% CI 28-48) in the 15 mg/kg ATLG group and 29% (20-40) in the 30 mg/kg ATLG group (hazard ratio [HR] 0·74, 95% CI 0·44-1·25; p=0·26). The cumulative incidence of non-relapse mortality was 9% (5-18) in the 15 mg/kg ATLG group and 19% (12-30) in the 30 mg/kg ATLG group (HR 2·08, 0·89-4·96; p=0·092). Cumulative incidence of disease recurrence was 15% (12-24): 14% (8-23) in the 15 mg/kg ATLG group versus 20% (13-31) in the 30 mg/kg ATLG group (HR 1·54, 0·74-3·21; p=0·25). The 5-year overall survival probability was 70% (62-77) for the whole study population: 78% (69-87) in the 15 mg/kg ATLG group versus 62% (50-73) in the 30 mg/kg ATLG group (HR 1·80, 1·01-3·20; p=0·045). The 5-year event-free survival was 77% for children in the 15 mg/kg ATLG group versus 61% in the 30 mg/kg ATLG group (HR 1·87, 1·07-3·28; p=0·028). INTERPRETATION: Children with haematological malignancies transplanted from unrelated donors selected through high-resolution HLA-typing benefit from the use of a 15 mg/kg ATLG dose in comparison with a 30 mg/kg ATLG dose. ATLG at 15 mg/kg should thus be regarded as the standard serotherapy regimen for unrelated donor allogeneic HSCT in this patient population. Future randomised studies will continue to aim to optimise patient outcome and strategies to prevent acute GVHD occurrence. FUNDING: Fresenius/Neovii Biotech.

Real-World Data for the Evaluation of Transarterial Radioembolization versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

OBJECTIVES: To perform a cost-effectiveness analysis comparing the use of transarterial radioembolization (TARE) with that of sorafenib in the treatment of patients with intermediate or advanced hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer staging system. METHODS: Patient-level data were consecutively recorded and collected at three oncology centers in Italy. A propensity score matching was performed to compare patients with similar clinical characteristics who underwent TARE or sorafenib treatment. Clinical data from the matched cohorts were used to populate a Markov model to project, on a lifetime horizon, life years, quality-adjusted life years, and economic outcomes associated with TARE and sorafenib for both intermediate and advanced HCC stages. RESULTS: Starting from data covering 389 and 241 patients who underwent TARE and sorafenib treatment, respectively, the propensity score matching yielded a total of 308 matched patients. For intermediate-stage patients, the model estimated for TARE versus sorafenib an incremental cost-utility ratio of €3,302/QALY (incremental cost-effectiveness ratio of €1,865 per life year gained), whereas for patients in advanced stage TARE dominated (lower costs and greater health improvements) compared with sorafenib. CONCLUSIONS: From an Italian health care service perspective, TARE could be a cost-effective strategy in comparison with sorafenib for patients with intermediate or advanced HCC. The results from forthcoming randomized controlled trials comparing TARE with sorafenib will be able to confirm or reject the validity of this preliminary evaluation. In the meantime, decision makers can use these results to control and coordinate the diffusion of the technology.

Intermittent catheterisation with hydrophilic and non-hydrophilic urinary catheters: systematic literature review and meta-analyses.

BACKGROUND: Intermittent catheterisation is the method of choice for the management of bladder dysfunctions. Different urinary catheters are available, but there is conflicting evidence on which type of catheter is best. The present study provides an objective evaluation of the clinical effectiveness of different subsets of urinary catheters. METHODS: A systematic literature review was performed for published RCTs regarding hydrophilic coated and PVC (standard) catheters for intermittent catheterisation. Separate meta-analyses were conducted to combine data on frequencies of urinary tract infections (UTIs) and haematuria. Two separate analyses were performed, including or excluding reused standard catheters. RESULTS: Seven studies were eligible for inclusion in the review. The meta-analyses exploring UTI frequencies showed a lower risk ratio associated with hydrophilic catheters in comparison to standard ones (RR = 0.84; 95% CI, 0.75-0.94; p = 0.003). Results for the "reuse" scenario were consistent with the ones related to "single-use" scenario in terms of frequency of UTIs. The meta-analyses exploring haematuria were not able to demonstrate any statistically significant difference between hydrophilic catheters in comparison to standard ones. CONCLUSIONS: The findings confirm previously reported benefits of hydrophilic catheters but a broader evaluation that takes into account also patient preferences, compliance of therapy, quality of life and costs would be needed to assess the economic sustainability of these advanced devices.

A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer.

The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods extend standard pairwise meta-analysis to allow simultaneous comparison of multiple treatments while maintaining randomization of individual studies. The method enables "direct" evidence (i.e., evidence from studies directly comparing two interventions) and "indirect" evidence (i.e., evidence from studies that do not compare the two interventions directly) to be pooled under the assumption of evidence consistency. We used NMA to evaluate progression-free survival (PFS) and time to progression (TTP) curves in 34 studies, and response rate (RR) and the hazard ratios (HRs) of the PFS/TTP in 36 studies. A number needed to treat (NNT) analysis was also performed as well as descriptive comparison of reported toxicities. The NMA for PFS/TTP curves and for HR shows EXE/EVE is more efficacious than capecitabine plus sunitinib, CMF, megestrol acetate and tamoxifen, with an average of related-PFS/TTP difference ranging from about 10 months for capecitabine plus sunitinib to more than 6 months for tamoxifen. The NMA for overall RR shows that EXE/EVE provides a better RR than bevacizumab plus capecitabine, capecitabine, capecitabine plus sorafenib, capecitabine plus sunitinib, CMF, gemcitabine plus epirubicin plus paclitaxel, EVE plus tamoxifen, EXE, FEC, megestrol acetate, mitoxantrone, and tamoxifen. Finally, the NMA for NNT shows that EXE/EVE is more beneficial as compared to BMF, capecitabine, capecitabine plus sunitinib, CMF, FEC, megestrol acetate, mitoxantrone, and tamoxifen. The combination of EXE/EVE as first- or second-line therapy for ER+ve/HER2-ve metastatic breast cancer is more efficacious than several chemotherapy regimens that were reported in the literature. Toxicities also favored EXE/EVE in most instances.

Edoxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis.

Edoxaban, an oral direct factor Xa inhibitor, has been found non-inferior to warfarin for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF), with a lower rate of intracranial bleeding. The aim of our investigation was to assess the cost-effectiveness of edoxaban versus warfarin from the perspective of the Italian health-care system. A Markov decision model was used to evaluate lifetime cost and quality-adjusted life expectancy of NVAF patients treated with warfarin or edoxaban. Transition probabilities were obtained from the ENGAGE AF-TIMI 48 trial, cost estimates were based on Italian prices and tariffs, utilities were obtained from the literature. One-way and second-order sensitivity analyses were performed. In the base case, lifetime costs were €18,658 for edoxaban and €14,060 for warfarin. Discounted quality-adjusted survival was 9.022 years for edoxaban and 8.425 years for warfarin, leading to an incremental cost-utility ratio of €7,713 per quality-adjusted life year (QALY) gained. Results were sensitive to time horizon, time in therapeutic range of warfarin and to the relative impact of warfarin versus edoxaban therapy onto quality of life. Probabilistic sensitivity analysis showed edoxaban to be cost-effective versus warfarin in 92.3 % of the simulations at a willingness-to-pay threshold of €25,000 per QALY. In conclusion, edoxaban proved to be a cost-effective alternative to warfarin in patients with moderate-to-high-risk NVAF.

The impact of recurrence of primary glomerulonephritis on renal allograft outcome.

Twenty-yr patient and death-censored graft survival of 348 kidney transplant recipients with primary glomerulonephritis (GN) and of 696 matched controls were 82.2% in GN patients and 75% in controls (p = 0.037) and 49.5% and 54%, respectively (p = 0.013). GN patients had a higher incidence of graft failure than controls even considering death as a competing risk (p = 0.004). In the GN group, graft survival of deceased and of living donor recipients was similar. At multivariate analysis, GN as primary disease (RR: 1.47), delayed graft function recovery (RR: 2.34), acute rejection (RR: 2.36), and any PRA positivity (RR: 1.01) were predictive of graft loss. GN recurred in 85 of 348 grafts (24.4%), and 43 were lost for recurrence. In non-recurrent patients, graft survival at 20 yr was significantly better than in recurrent patients (59.4% vs. 24.4%, p = 0.000), but not different from that of controls (59.4 vs. 54%, p = 0.9). At multivariate analysis, young age at transplantation (RR: 0.97), shorter duration of dialysis (RR: 1.05 per each dialysis year), and graft from living donors (RR: 1.668) were independent predictors of recurrence. Patients with primary GN have reduced graft survival in comparison with controls, and this is mainly due to recurrence of original disease. However, the most frequent recurrence in living recipients does not compromise graft survival.

Cost-Effectiveness Analysis of HRD Testing for Previously Treated Patients with Advanced Ovarian Cancer in Italy.

INTRODUCTION: Ovarian cancer (OC) is the eighth most common cancer among women, and homologous recombination deficiency (HRD) is present in approximately 50% of these patients. For this group, poly(ADP-ribose) polymerase (PARP) inhibitors are more likely to be effective. The aim of the study was to investigate the cost-effectiveness of HRD testing versus BRCA testing (which identifies mutations present only in 25% of patients) in Italy to optimize the treatment management, possibly with PARP inhibitors. METHODS: A cost-effectiveness partition survival model was developed to estimate the expected costs and outcomes (life years, LYs; quality-adjusted life years, QALYs) with lifetime horizon of HRD testing versus BRCA testing alone in women with high-grade serous or endometrioid advanced ovarian cancer. The option to perform the tests in sequence, that is, the BRCA test followed by the HRD test, in patients with BRCA-negative test was also considered, and the model accounted for the National Healthcare Service (NHS) perspective in Italy. The treatments represented the best available options according to the initial test results and according to PARP inhibitors available in Italy. A 3% discount rate was applied. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model results. RESULTS: HRD testing was shown to be a cost-effective strategy compared to BRCA testing (incremental cost-utility ratio 22,610€/QALY) and a cost-saving strategy compared to the sequence of tests. The probabilistic sensitivity analysis showed that the HRD test is cost-effective compared to BRCA testing in 98.5% of model simulations considering a willingness-to-pay threshold of 50,000€/QALY. CONCLUSION: The identification of genetic anomalies in patients with advanced OC is a costly process. Regardless, HRD upfront testing compared to BRCA testing had a cost-effective profile, allowing the efficient use of healthcare resources and better life expectancy and quality of life for patients.

Ovarian cancer has been the most lethal gynecological tumor for years. Recently, there have been notable advances due to the introduction of poly(adenosine diphosphate-ribose polymerase) (PARP) inhibitor drugs, which have significantly increased the survival rates of women affected by advanced-stage disease. At least 50% of ovarian tumors have a defect in the DNA repair mechanism, known as homologous recombination deficiency, and the mechanism of action of these drugs involves blocking the DNA repair mechanisms implemented by neoplastic cells. The identification of patients with homologous recombination deficiency through a genetic test, with consequent optimized treatment management, possibly with PARP inhibitors, resulted in better life expectancy, even when adjusted for the quality of life, than the management of patients starting from BRCA testing alone. The homologous recombination deficiency testing strategy can be considered cost-effective from the National Healthcare Service perspective in Italy. These findings provide evidence of the value of a new diagnostic option for clinicians and payers to optimize the management of women with high-grade serous or endometrioid advanced ovarian cancer.

Economic value of diastasis repair with the use of mesh compared to no intervention in Italy.

AIM: Rectus abdominal diastasis (RAD) can cause mainly incontinence and lower-back pain. Despite its high incidence, there is no consensus regarding surgical indication. We aimed at comparing RAD repair (minimally invasive technique with mesh implant) with no treatment (standard of care - SOC) through cost-effectiveness and budget impact analyses from both National Healthcare Service (NHS) and societal perspectives in Italy. METHODS: A model was developed including social costs and productivity losses derived by the online administration of a socio-economic questionnaire, including the EuroQol for the assessment of quality of life. Costs for the NHS were based on reimbursement tariffs. RESULTS: Over a lifetime horizon, estimated costs were 64,115€ for SOC and 46,541€ for RAD repair in the societal perspective; QALYs were 19.55 and 25.75 for the two groups, respectively. Considering the NHS perspective, RAD repair showed an additional cost per patient of 5,104€ compared to SOC, leading to an ICUR of 824€. RAD repair may be either cost-saving or cost-effective compared to SOC depending on the perspective considered. Considering a current scenario of 100% SOC, an increased diffusion of RAD repair from 2 to 10% in the next 5 years would lead to an incremental cost of 184,147,624€ for the whole society (87% borne by the NHS) and to incremental 16,155 QALYs. CONCLUSION: In light of the lack of economic evaluations for minimally invasive RAD repair, the present study provides relevant clinical and economic evidence to help improving the decision-making process and allocating scarce resources between competing ends.

Systematic review for the development of a core outcome set for monofocal intraocular lenses for cataract surgery.

Introduction: The aim of the study was to define a core outcome set (COS) to be measured following cataract surgery for the postoperative evaluation of monofocal intraocular lenses (IOLs). Compared to current COSs, the present work provides updates considering the advances in the technology due to the development of new generation monofocal IOLs, which are characterized by a safety profile comparable to standard monofocal IOLs but with an extended range of intermediate vision. Methods: Healthcare professionals (ophthalmologist surgeons) and patients were involved in the selection of outcomes to be included in the COS, starting from a list of indicators retrieved from a systematic literature search. The search considered observational studies with both a retrospective or prospective design, case studies and classic randomized controlled trials (RCTs). A mixed methodology integrating a Delphi-driven and an expert panel approach was adopted to reach an agreement among clinicians, while patients were involved in the completion of a questionnaire. Results: The final COS included 15 outcomes. Eleven outcomes, all clinical, were considered for inclusion after a joint discussion among ophthalmologists; seven outcomes were linked to visual acuity, while the remaining to contrast sensitivity, refractive errors, aberrations and adverse events. Measurement metrics, method of aggregation and measurement time point of these outcomes were specified. The most important aspects for the patients were (1) quality of life after cataract surgery, (2) the capacity to perform activities requiring good near vision (e.g., reading), (3) spectacle independence, and (4) safety of movements without fear of getting hurt or falling (intermediate vision). Discussion: In a context with limited healthcare resources, it is important to optimize their use considering also the preferences of end-users, namely patients. The proposed COS, developed involving both ophthalmologists and patients, provides an instrument for the postoperative evaluation of different technologies in the context of monofocal IOLs, which can be used not only in clinical trials but also in clinical practice to increase the body of real-world evidence.

Is precision medicine the solution to improve organ preservation in laryngeal/hypopharyngeal cancer? A position paper by the Preserve Research Group.

In locally advanced (LA) laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC), larynx preservation (LP) strategies aim at the cure of the disease while preserving a functional larynx, thus avoiding total laryngectomy and the associated impact on the quality of life. In the last decades, apart from transoral and open-neck organ preservation approaches, several non-surgical regimens have been investigated: radiotherapy alone, alternate, concurrent or sequential chemoradiation, and bioradiotherapy. Despite major progress, the identification of reliable and effective predictors for treatment response remains a clinical challenge. This review examines the current state of LP in LA-LHSCC and the need for predictive factors, highlighting the importance of the PRESERVE trial in addressing this gap. The PRESERVE trial represents a pivotal initiative aimed at finding the optimal therapy for laryngeal preservation specific to each patient through a retrospective analysis of data from previous LP trials and prospectively validating findings. The goal of the PRESERVE trial is to develop a comprehensive predictive classifier that integrates clinical, molecular, and multi-omics data, thereby enhancing the precision and efficacy of patient selection for LP protocols.

Impella versus VA-ECMO for the treatment of patients with cardiogenic shock: the Impella Network Project - observational study protocol for cost-effectiveness and budget impact analyses.

INTRODUCTION: The treatment of patients with cardiogenic shock (CS) encompasses several health technologies including Impella pumps and venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, while they are widely used in clinical practice, information on resource use and quality of life (QoL) associated with these devices is scarce. The aim of this study is, therefore, to collect and comparatively assess clinical and socioeconomic data of Impella versus VA-ECMO for the treatment of patients with severe CS, to ultimately conduct both a cost-effectiveness (CEA) and budget impact (BIA) analyses. METHODS AND ANALYSIS: This is a prospective plus retrospective, multicentre study conducted under the scientific coordination of the Center for Research on Health and Social Care Management of SDA Bocconi School of Management and clinical coordination of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute in Milan. The Impella Network stemmed for the purposes of this study and comprises 17 Italian clinical centres from Northern to Southern Regions in Italy. The Italian network qualifies as a subgroup of the international Impella Cardiac Surgery Registry. Patients with CS treated with Impella pumps (CP, 5.0 or 5.5) will be prospectively recruited, and information on clinical outcomes, resource use and QoL collected. Economic data will be retrospectively matched with data from comparable patients treated with VA-ECMO. Both CEA and BIA will be conducted adopting the societal perspective in Italy. This study will contribute to generate new socioeconomic evidence to inform future coverage decisions. ETHICS AND DISSEMINATION: As of May 2024, most of the clinical centres submitted the documentation to their ethical committee (N=13; 76%), six centres received ethical approval and two centres started to enrol patients. Study results will be published in peer-reviewed publications and disseminated through conference presentations.

No difference in outcome between children and adolescents transplanted for acute lymphoblastic leukemia in second remission.

Acute lymphoblastic leukemia (ALL) in second complete remission is one of the most common indications for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. We compared the outcome after HCST of adolescents, aged 14 to 18 years, with that of children (ie, patients < 14 years of age). Enrolled in the study were 395 patients given the allograft between January 1990 and December 2007; both children (334) and adolescents (61) were transplanted in the same pediatric institutions. All patients received a myeloablative regimen that included total body irradiation in the majority of them. The donor was an HLA-identical sibling for 199 patients and an unrelated volunteer in the remaining 196 patients. Children and adolescents had a comparable cumulative incidence of transplantation-related mortality, disease recurrence, and of both acute and chronic graft-versus-host disease. The 10-year probability of overall survival and event-free survival for the whole cohort of patients were 57% (95% confidence interval, 52%-62%) and 54% (95% confidence interval, 49%-59%), respectively, with no difference between children and adolescents. This study documents that adolescents with ALL in second complete remission given HSCT in pediatric centers have an outcome that does not differ from that of patients younger than 14 years of age.

Hematopoietic stem cell transplantation for children with high-risk acute lymphoblastic leukemia in first complete remission: a report from the AIEOP registry.

Children with high-risk acute lymphoblastic leukemia in first complete remission can benefit from allogeneic hematopoietic stem cell transplantation. We analyzed the outcome of 211 children with high-risk acute lymphoblastic leukemia in first complete remission who were given an allogeneic transplant between 1990 and 2008; the outcome of patients who, despite having an indication for transplantation and a suitable donor, did not receive the allograft for different reasons in the same time period was not analyzed. Sixty-nine patients (33%) were transplanted between 1990 and 1999, 58 (27%) between 2000 and 2005, and 84 (40%) between 2005 and 2008. A matched family donor was employed in 138 patients (65%) and an unrelated donor in 73 (35%). The 10-year probabilities of overall and disease-free survival were 63.4% and 61%, respectively. The 10-year cumulative incidences of transplantation-related mortality and relapse were 15% and 24%, respectively. After 1999, no differences in either disease-free survival or transplant-related mortality were observed in patients transplanted from unrelated or matched family donors. In multivariate analysis, grade IV acute graft-versus-host disease was an independent factor associated with worse disease-free survival. By contrast, grade I acute graft-versus-host disease and age at diagnosis between 1 and 9 years were favorable prognostic variables. Our study, not intended to evaluate whether transplantation is superior to chemotherapy for children with acute lymphoblastic leukemia in first complete remission and high-risk features, shows that the allograft cured more than 60% of these patients; in the most recent period, the outcome of recipients of grafts from matched family and unrelated donors was comparable.

Cost-Utility Analysis of Esketamine for Patients with Treatment-Resistant Depression in Italy.

AIM: Major depressive disorder is considered one of the most frequent diseases in the general population, and treatment-resistant depression (TRD) represents the subset with more significant clinical and social impact. Large, robust phase III studies have shown safety and efficacy of esketamine nasal spray plus SSRI/SNRI antidepressants (ADs) compared with SSRI/SNRI plus placebo nasal spray in patients with TRD. The main aim of this study was to perform a cost-utility analysis comparing esketamine plus ADs with ADs alone in TRD patients, from the societal perspective in Italy. A secondary analysis focused on the National Healthcare Service (NHS) perspective. METHODS: A Markov multistate model has been developed to estimate quality-adjusted life years and economic outcomes of both treatment strategies over 5 years considering the initiation of esketamine in the different treatment lines, from 3 to 5 (3L-5L). The model has been populated with data from literature and real-world evidence. The analysis from the societal perspective considered direct healthcare costs and patients' productivity losses. In addition to the incremental cost-utility ratio (ICUR), the incremental net monetary benefit (INMB) has been calculated as (incremental benefit × WTP) - incremental cost and by applying a willingness-to-pay (WTP) of 50,000€/QALY. Deterministic and probabilistic sensitivity analyses have been performed to assess the robustness of the model results. RESULTS: From the societal perspective, the ICUR ranged between 16,314€ and 22,133€ per QALY according to the different treatment lines, while it was over the threshold of 100,000€/QALY for the NHS perspective. The INMB was positive and ranged from 2259€ to 2744€ across treatment lines in the societal perspective; the INMB begins to occur earlier when moving towards subsequent lines of treatment (3.9 years for 3L, 3.6 years for 4L and 3.5 years for 5L). The analyses showed also that the advantage in terms of INMB is maintained for a wide range of societal preferences expressed by WTP thresholds, and in particular for values above 22,200€, 16,400€ and 17,100€ for 3L, 4L and 5L, respectively. CONCLUSION: The study showed that esketamine may be a cost-effective opportunity from the societal perspective for the management of patients with treatment-resistant depression. In the future, data collected from observational studies or registries, which can include the collection of productivity losses and also costs sustained by the patients, will be able to provide further evidence in order to improve the reliability of the model results.