Venous thrombo-embolism (VTE) prevention of patients undergoing total hip and knee replacement: budget impact analysis of apixaban in Italy

BACKGROUND: Venous thromboembolism (VTE) is a common and burdensome cardiovascular condition, frequently leading to severe complications and requiring high-cost healthcare interventions. New oral anticoagulants (nOACs) have demonstrated to be efficacious and safe in VTE prevention of patients undergoing total hip replacement (THR) and total knee replacement (TKR), a condition that is typically associated to cardiovascular disease. The Italian Healthcare Service (SSN) has recently approved the latest nOAC, apixaban. The present article aims to evaluate its economic impact in the perspective of the Italian SSN.METHODS: We conducted a budget impact analysis to estimate clinical outcomes and economic consequences associated to the reimbursement of apixaban, in the prevention of VTE as a consequence of major orthopedic surgery, over a three-year time horizon. In our analysis we compared two alternative scenarios, with apixaban either reimbursed (Scenario B) or not reimbursed (Scenario A) by the Italian SSN, and estimated the difference of healthcare costs between the two scenarios. Only direct healthcare costs have been considered.RESULTS: According to market assumptions, it is estimated that 1.2%, 3.7%, and 6.5% of THR patients, and 1.2%, 3.8% and 6.7% of TKR patients, would be treated with apixaban over the first three years since launch. At the estimated daily cost of apixaban (€2.48/die), this would translate into a budget impact of €14.3 mln, €45.5 mln, and €81.4 mln at years 1, 2 and 3 since launch, respectively. This expenditure would be more than offset by savings, due to: i) reduction of prescriptions of alternative treatment options (other nOACs, low-molecular weight heparins, fondaparinux); ii) reduction of the economic burden attributable of CV complications of VTE. Finally, Scenario B resulted slightly favourable compared to Scenario A, leading to economic savings for about €50 thousands over three years. Sensitivity analyses confirmed findings of the base-case analysis.CONCLUSIONS: Reimbursement of apixaban does not determine a budget impact increase for Italian SSN. Its usage may be considered fully sustainable from a pharmaco-economic viewpoint

The Importance of Real-World Evidence in Understanding Influenza Vaccine Effectiveness

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Health Technology Assessment on the use of the Wearable Cardioverter Defibrillator in Patients with Myocardial Infarction and with ICD Explant

The objective of the present work is to conduct a Health Technology Assessment (HTA) on the use of the Wearable Cardioverter Defibrillator (WCD) in patients at risk of Sudden Cardiac Arrest (SCA) following Myocardial Infarction (MI) or with an explanted Implantable Cardioverter Defibrillator (ICD)

Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective

BACKGROUND: Delayed-release dimethyl fumarate (also known as gastro-resistant dimethyl fumarate, hereafter dimethyl fumarate) is an oral disease-modifying therapy used for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS), an autoimmune chronic inflammatory condition of the central nervous system.OBJECTIVE: The objective of this economic analysis was to compare cost-effectiveness of dimethyl fumarate with the alternatives used as first-line treatment of RRMS in Italy.METHODS: The analysis was conducted from the Italian societal perspective. Health outcomes and costs were evaluated over a 50-year time horizon (equivalent to a lifetime horizon). Both health outcomes and costs were discounted at 3.5%. The cost-effectiveness analysis was conducted by adapting a Markov model, already used in previous similar economic analyses conducted in RRMS, to the Italian context. The Markov model estimated the clinical and economic consequences of treating RRMS patients with the following therapeutic options: dimethyl fumarate; interferon (IFN) beta-1a subcutaneous (SC) at two different doses, 22 mcg and 44 mcg; IFN beta-1b SC; glatiramer acetate (GA) SC 20 mg; oral teriflunomide. Clinical efficacy data were retrieved from an elaboration of an already published mixed treatment comparison (MTC). Both direct and indirect costs (disability, treatment acquisition, administration, monitoring, relapses, adverse events) were included in the analysis. One-way and probabilistic sensitivity analyses were carried out and cost-effectiveness acceptability curves generated.RESULTS: In the base-case analysis, dimethyl fumarate was more efficacious than alternatives, in terms of both survival (19.634 vs. 19.440-19.600 life years for alternatives), and quality-of-life-adjusted survival (6.526 vs. 5.143- 6.189 QALYs for alternatives). The total lifetime cost per patient treated with dimethyl fumarate (€ 954,286) was lower than that of the other DMTs included in the analysis. Therefore, dimethyl fumarate was dominant compared with all analyzed alternatives. Dimethyl fumarate was also the therapeutic option with the highest benefit on disease burden. In fact, costs of disability management were lower than those of all the other first-line drugs included in the analysis. The results of one-way deterministic sensitivity analysis and probabilistic sensitivity analysis confirmed the reliability of base-case results.CONCLUSIONS: The results of the cost-effectiveness analysis confirm that dimethyl fumarate is an optimal first-line treatment for RRMS in Italy, compared with the other first-line alternatives included in the economic analysis, when evaluated from the societal perspective

Critical Review of the Pivotal Studies of Four rFVIII Products for the Treatment of Hemophilia A Patients: The Role of Octocog Alfa

INTRODUCTION: Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of clotting factor VIII (FVIII). The severe form of the disease is characterized by spontaneous bleeds, especially into the joints. Prophylaxis, based on regularly intravenous administration of the missing factor to avoid hemorrhages, represents the gold standard of treatment. In recent years, new products that significantly improve the treatment management options for patients with hemophilia have become available in the market.OBJECTIVE: To critically evaluate the pivotal studies of recombinant FVIII (rFVIII) products, approved in Europe within the first half of 2018 having obtained the indication for a prophylaxis dosing regimen based also on a twice weekly infusion frequency or even less, highlighting their limitations or strengths.METHODS: A systematic literature search was conducted, and several databases (PubMed and Embase) were consulted.RESULTS: Nine clinical trials involving patients with severe hemophilia A without inhibitor were included in this analysis. Four rFVIII products (Elocta®, Biogen, Cambridge, MA, USA; Kovaltry®, Bayer HealthCare Pharmaceuticals, Germany; Afstyla®, CSL Behring GmbH, Germany; Adynovi®, Baxalta Innovation GmbH, Austria) with different pharmacokinetic profiles were evaluated. The trials included in this analysis had different designs and heterogeneous methods were utilized to assess the study outcomes. The baseline characteristics of the patients enrolled in the studies were also often different and sometimes not adequately described. LEOPOLD II, a trial to compare prophylaxis to on-demand therapy with an unmodified rFVIII product (Kovaltry®, octocog alfa), was the only completely randomized trial that enrolled a more critical patient population in terms of compromised joint condition than the other studies. Based on these side-by-side comparison, Octocog alfa reported similar efficacy, in terms of annualized bleeding rate, to the other rFVIII products, including extended half-life.CONCLUSIONS: Even without structural modifications, octocog alfa may be considered a useful treatment option for two times a week prophylaxis in a selected population of haemophilia patients

Cost Minimization Analysis of Radiofrequency Compared to Laser Thermal Ablation in Patients with Hepatocellular Carcinoma

BACKGROUND: Over the last decade of years, minimally invasive techniques have been developed for the treatment of hepatocellular carcinoma and liver metastases. We sought to investigate the health costs associated with the management of patients with hepatocellular carcinoma treated with radiofrequency vs laser thermal ablation and their clinical outcomes.METHODS: We performed a retrospective analysis of the ablations performed in two referral centers in southern Italy, from 2009 to 2013. Resource use was valued by year 2017 official prices, in €. Direct healthcare costs (drugs, visits, tests and hospitalizations) of different ablation techniques were compared. Total costs were analyzed from Italian NHS perspective.RESULTS: A total of 140 patients were identified. Baseline demographics and clinical outcomes of interest did not differ between the two groups. Patients treated with laser thermal ablation resulted in an expected annually cost savings of 258.9 € per patient, in one-year follow-up healthcare costs compared with radiofrequency. The largest components of annual medical expenditures were attributable to drugs, regardless of the type of ablative technique.CONCLUSIONS: The ablation using either laser thermal ablation or radiofrequency is equally effective. Laser thermal ablation would carry disposable cost savings as compared to radiofrequency. The costs associated with management of patients with hepatocellular carcinoma, treated with laser thermal ablation were lower than those treated with radiofrequency ablation

Efficiency measures of emergency departments: an Italian systematic literature review

Life expectancy globally increased in the last decades: the number of people aged 65 or older is consequently projected to grow, and healthcare demand will increase as well. In the recent years, the number of patients visiting the hospital emergency departments (EDs) rocked in almost all countries of the world. These departments are crucial in all healthcare systems and play a critical role in providing an efficient assistance to all patients. A systematic literature review covering PubMed, Scopus and the Cochrane Library was performed from 2009 to 2019. Of the 718 references found in the literature research, more than 25 studies were included in the current review. Different predictors were associated with the quality of EDs care, which may help to define and implement preventive strategies in the near future. There is no harmonisation in efficiency measurements reflecting the performance in the ED setting. The identification of consistent measures of efficiency is crucial to build an evidence base for future initiatives. The aim of this study is to review the literature on the problems encountered in the efficiency of EDs around the world in order to identify an organisational model or guidelines that can be implemented in EDs to fill inefficiencies and ensure access optimal treatment both in terms of resources and timing. This review will support policy makers to improve the quality of health facilities, and, consequently of the entire healthcare systems

[Budget impact analysis of idarucizumab for the management of patients treated with dabigatran in emergency / urgent situations in Italy]

BACKGROUND: Each drug therapy with an anticoagulant effect may require, in emergency conditions, a rapid and specific strategy for a prompt restoration of coagulation. Dabigatran is the first-in-class of the so-called new oral anticoagulants (NAO), that have been made available in recent years in addition to traditionally-used vitamin K antagonists (VKA). Idarucizumab is a monoclonal antibody that binds to dabigatran, neutralizing its anticoagulant effect.OBJECTIVE: To assess the economic effect of idarucizumab in patients treated with dabigatran when the rapid reversal of its anticoagulant effect is required.METHODS: The analysis was carried over through the development of a budget impact model specifically adapted to the context of Italian care. The analysis was conducted along a time horizon of five years. The target population was defined by those patients on dabigatran treatment presenting uncontrolled and life-threatening bleedings (gastro-intestinal, intracranial or other) or requiring emergency surgery or urgent procedures. The estimation of healthcare resources (i.e. diagnostic procedures, medications, and other in-hospital services) needed for the management of uncontrolled bleeding and emergency surgery in patients treated with dabigatran was obtained from a panel of five Italian Clinical Experts. Unit costs were derived from current prices and tariffs.RESULTS: The total cost of management with the current therapeutic modalities ranged from € 16.5 million in year 1 to € 20.1 million in year 5. In the scenario with idarucizumab the total cost ranged from € 15.4 million in year 1 to € 18.7 million in year 5. The adoption of idarucizumab resulted in a cumulative 5-year savings of 6.5 million euro corresponding to 7.1% of the total expense.CONCLUSION: Idarucizumab for the management of patients treated with dabigatran in emergency / urgent situations has the potential for substantial savings, compared to treatments currently available. This preliminary assessment will require further confirmatory evidence when the product will become available in Italian healthcare setting.[Article in Italian

Obsessive Compulsive Tic Disorder: appropriate diagnosis and treatment as key elements to improve health and rationalize use of resources

Background: Obsessive Compulsive Tic Disorder (OCTD) has been described recently as an early onset and highly disabling endophenotype of Tic Disorder and Obsessive Compulsive Disorder. OCTD has a relevant but largely unknown clinical, social and economic burden for patients and their families. Our paper aimed to explore relevant aspects of the burden of OCTD. Methods: we conducted a literature review and a pilot study using retrospective demographic, clinical and economic data of patients with OCTD accessing the Galeazzi Hospital in Milan. Results: the literature review shows the absence of information on OCTD. From the pilot study we analysed data of 30 patients (80.0% male, 36.7% aged from 7 to 13 years, 63.3% aged from 15 to 48 years), 83.0% declared that obsessions and/or compulsions were the most important factors determining their social impairment. Adult patients refractory to drug treatment underwent Deep Brain Stimulation plus drugs. The mean clinical scores at the time of diagnosis indicated a severe condition for both tics and obsessive compulsive components. The mean time elapsed from symptoms onset to diagnosis of OCTD was 5.6 years, reaching up to 11 years in one case. Before reaching the correct diagnosis, different specialists visited the patients several times, 93.3% underwent diagnostic examinations and 86.7% took 2 or 3 different drugs. Ten patients were hospitalised and 8 had received psychotherapy. Discussion: Albeit preliminary, these results show that attention is mandatory for establishing correct diagnosis and treatment guidelines to improve health and rationally spend resources for OCTD

[Cost-effectiveness analysis of ocriplasmin in the treatment of vitreomacular traction in Italy]

BACKGROUND: Vitreomacular traction (VMT) caused by vitreomacular adhesion (VMA), is a pathological condition when the vitreous humor has an abnormally strong attachment to the central part of the retina. Ocriplasmin recently approved for the treatment of VMT, including when associated with macular hole (MH) of diameter less than or equal to 400 microns, is a recombinant truncated form of the human serine protease plasmin with retained enzymatic activity, administered by intravitreal injection. We estimated long-term benefits and costs associated with the resolution of traction, following treatment with ocriplasmin versus Standard of Care (SoC), from National Health Service (NHS) perspective.METHODS: A lifetime Markov model has been adopted for Italy in order to estimate costs and outcomes, gained for patients with VMT, with and without MH, treated with ocriplasmin. Health effects have been expressed as Life Years (LY) and Quality adjusted LY gained (QALY), and estimated based on time spent in Visual Acuity (VA) states, defined by best and worst seeing eye, disutility impact associated with surgical interventions, adverse events and metamorphopsia. Deterministicand probabilistic analysis have also been conducted.RESULTS: Over a lifetime ocriplasmin versus SoC generated incremental benefits in terms of QALYs and overall treatment costs in each patients subgroups. Patients with VMT and VMT+MH treated with ocriplasmin had an incremental survival benefits of 0.1123 and 0.0772 QALYs respectively. Therefore, it is expected to come at an incremental cost of 1,873 € and 2,185 € for VMT and VMT+MH patients respectively. The associated ICER is 16,683 € and 28,294 € per QALY gained. Both sensitivity analyses for each of the subgroups confirmed the robustness of the model results.CONCLUSION: Compared to SoC, ocriplasmin is a cost effective therapy option in the treatment of VMT, including whenassociated with MH.[Article in Italian