Towards Resilient Healthcare Systems: A Framework for Crisis Management.

This study addresses the crucial need for resilient healthcare systems, highlighted by recent global health emergencies such as the Ebola and COVID-19 crises. It identifies a significant gap in the current literature: a lack of practical, actionable frameworks for healthcare resilience. To bridge this gap, the research introduces an innovative framework that blends theoretical resilience concepts with heuristic approaches. This framework, rooted in the principles of monitoring, anticipation, recognition, and learning, is designed to enhance the crisis management capabilities of healthcare systems. The methodology involves a comprehensive literature review, combined with heuristic methods, culminating in a framework that is both academically sound and practically applicable. This framework guides healthcare systems through various stages of crisis management, including data collection, situation analysis, risk anticipation, and response evaluation. It provides a holistic approach to enhancing resilience in healthcare settings. Overall, this paper makes a significant contribution to the field of healthcare system resilience, offering a strategic blueprint for improved crisis response and recovery. It marks an important advancement in aligning theoretical resilience concepts with practical implementation strategies, essential for tackling current and future healthcare challenges.

Cost-Effectiveness of Treatment Optimisation with Biomarkers for Immunotherapy in Solid Tumours: A Systematic Review.

This study investigated the health economic evaluations of predictive biomarker testing in solid tumours treated with immune checkpoint inhibitors (ICIs). Searching PubMed, EMBASE, and Web of Science from June 2010 to February 2022, 58 relevant articles were reviewed out of the 730 screened. The focus was predominantly on non-small cell lung cancer (NSCLC) (65%) and other solid tumours (40%). Among the NSCLC studies, 21 out of 35 demonstrated cost-effectiveness, notably for pembrolizumab as first-line treatment when preceded by PD-L1 assessment, cost-effective at a threshold of $100,000/QALY compared to the standard of care. However, for bladder, cervical, and triple-negative breast cancers (TNBCs), no economic evaluations met the affordability threshold of $100,000/QALY. Overall, the review highlights a certain degree of uncertainty about the cost-effectiveness of ICI. In particular, we found PD-L1 expression associated with ICI treatment to be a cost-effective strategy, particularly in NSCLC, urothelial, and renal cell carcinoma. The findings suggest the potential value of predictive biomarker testing, specifically with pembrolizumab in NSCLC, while indicating challenges in achieving cost-effectiveness for certain other solid tumours.

A cost-of-illness study of Behçet syndrome in Italy.

OBJECTIVE: This study aims at evaluating the cost-of-illness (COI) of patients diagnosed with Behcet's syndrome (BS) in Italy, trying to depict the impact of different costs' components to the overall economic burden and analysing the variability of costs according to years since diagnosis and age at first symptoms. METHODS: With a cross-sectional evaluation, we surveyed a large sample of BS patients in Italy assessing several dimensions related to BS, also including fact related to the use of health resources utilization, formal and informal care, and productivity losses. Overall costs, direct health, direct non-health, and indirect costs were thus estimated per patient/year considering a Societal perspective and the impact of years since diagnosis, age at first symptoms on costs was evaluated using generalized linear model (GLM) and a two-part model, adjusting for age and distinguishing among employed and non-employed responders. RESULTS: A total of 207 patients were considered in the present study. From the perspective of the Society, mean overall costs for BS patient were estimated to be 21,624 € (0;193,617) per patient/year. Direct non-health expenses were the main costs component accounting for 58% of the overall costs, followed direct health costs, 36%, while indirect costs because of productivity losses represented 6% of the overall costs. Being employed resulted in significantly lower overall costs (p = 0.006). Results from the multivariate regression analyses suggested that the probability of incurring in overall costs equal to zero decreased as time from BS diagnosis is 1 year or more as compared to newly diagnosed patients (p < 0.001); while among those incurring in expenses, costs decreased for those experiencing first symptoms between 21 and 30 years (p = 0.027) or later (p = 0.032) as compared to those having symptoms earlier. Similar findings emerged among the subgroups of patients declaring themselves as workers, while no impact of years since diagnosis or age of first symptoms was found among non-workers. CONCLUSIONS: The present study offers a comprehensive overview of the economic consequences imposed by BS in a societal perspective, providing insights into the distribution of the different costs component related to BS, thus helping the development of targeted policies.

Drug-Utilization, Healthcare Facilities Accesses and Costs of the First Generation of JAK Inhibitors in Rheumatoid Arthritis.

This study is aimed at describing tofacitinib and baricitinib users by characterizing their prescription and healthcare histories, drug and healthcare utilization patterns, and direct costs from a healthcare system perspective. This retrospective cohort study was performed using Tuscan administrative healthcare databases, which selected two groups of Janus kinase inhibitors (JAKi) incident users (index date) from 1st January 2018 to 31 December 2019 and from 1 January 2018 to 30 June 2019. We included patients ≥18 years old, at least 10 years of data, and six months of follow-up. In the first analysis, we describe mean time, standard deviation (SD), from the first-ever disease-modifying antirheumatic drug (DMARD) to the JAKi, and costs of healthcare facilities and drugs in the 5 years preceding the index date. In the second analysis, we assessed Emergency Department (ED) accesses and hospitalizations for any causes, visits, and costs in the follow-up. In the first analysis, 363 incident JAKi users were included (mean age 61.5, SD 13.6; females 80.7%, baricitinib 78.5%, tofacitinib 21.5%). The time to the first JAKi was 7.2 years (SD 3.3). The mean costs from the fifth to the second year before JAKi increased from 4325 € (0; 24,265) to 5259 € (0; 41,630) per patient/year, driven by hospitalizations. We included 221 incident JAKi users in the second analysis. We observed 109 ED accesses, 39 hospitalizations, and 64 visits. Injury and poisoning (18.3%) and skin (13.8%) caused ED accesses, and cardiovascular (69.2%) and musculoskeletal (64.1%) caused hospitalizations. The mean costs were 4819 € (607.5; 50,493) per patient, mostly due to JAKi. In conclusion, the JAKi introduction in therapy occurred in compliance with RA guidelines and the increase in costs observed could be due to a possible selective prescription.

Socioeconomic inequalities in cancer mortality between and within countries in Europe: a population-based study.

Background: Reducing socioeconomic inequalities in cancer is a priority for the public health agenda. A systematic assessment and benchmarking of socioeconomic inequalities in cancer across many countries and over time in Europe is not yet available. Methods: Census-linked, whole-of-population cancer-specific mortality data by socioeconomic position, as measured by education level, and sex were collected, harmonized, analysed, and compared across 18 countries during 1990-2015, in adults aged 40-79. We computed absolute and relative educational inequalities; temporal trends using estimated-annual-percentage-changes; the share of cancer mortality linked to educational inequalities. Findings: Everywhere in Europe, lower-educated individuals have higher mortality rates for nearly all cancer-types relative to their more highly-educated counterparts, particularly for tobacco/infection-related cancers [relative risk of lung cancer mortality for lower- versus higher-educated = 2.4 (95% confidence intervals: 2.1-2.8) among men; = 1.8 (95% confidence intervals: 1.5-2.1) among women]. However, the magnitude of inequalities varies greatly by country and over time, predominantly due to differences in cancer mortality among lower-educated groups, as for many cancer-types higher-educated have more similar (and lower) rates, irrespective of the country. Inequalities were generally greater in Baltic/Central/East-Europe and smaller in South-Europe, although among women large and rising inequalities were found in North-Europe (relative risk of all cancer mortality for lower- versus higher-educated ≥1.4 in Denmark, Norway, Sweden, Finland and the England/Wales). Among men, rate differences (per 100,000 person-years) in total-cancer mortality for lower-vs-higher-educated groups ranged from 110 (Sweden) to 559 (Czech Republic); among women from approximately null (Slovenia, Italy, Spain) to 176 (Denmark). Lung cancer was the largest contributor to inequalities in total-cancer mortality (between-country range: men, 29-61%; women, 10-56%). 32% of cancer deaths in men and 16% in women (but up to 46% and 24%, respectively in Baltic/Central/East-Europe) were associated with educational inequalities. Interpretation: Cancer mortality in Europe is largely driven by levels and trends of cancer mortality rates in lower-education groups. Even Nordic-countries, with a long-established tradition of equitable welfare and social justice policies, witness increases in cancer inequalities among women. These results call for a systematic measurement, monitoring and action upon the remarkable socioeconomic inequalities in cancer existing in Europe. Funding: This study was done as part of the LIFEPATH project, which has received financial support from the European Commission (Horizon 2020 grant number 633666), and the DEMETRIQ project, which received support from the European Commission (grant numbers FP7-CP-FP and 278511). SV and WN were supported by the French Institut National du Cancer (INCa) (Grant number 2018-116). PM was supported by the Academy of Finland (#308247, # 345219) and the European Research Council under the European Union's Horizon 2020 research and innovation programme (grant agreement No 101019329). The work by Mall Leinsalu was supported by the Estonian Research Council (grant PRG722).

The Current Burden of Oropharyngeal Cancer: A Global Assessment Based on GLOBOCAN 2020.

BACKGROUND: Oropharyngeal cancer (OPC) is a complex disease whose etiologies, either related to risk factors such as smoking or alcohol, or linked to HPV infection, are believed to be responsible for wide gender and geographical variability. This study depicts the current burden of OPC worldwide. METHODS: Estimated OPC new cases, deaths, age-standardized rates (ASR) for both incidence and mortality in 2020 were obtained from the GLOBOCAN database for each country and across 20 UN-defined world regions by sex. The incidence-to-mortality ratio (IMR) was also estimated from ASR. RESULTS: Worldwide, 98,400 new cases and 48,100 OPC deaths were estimated in 2020, with ASR of 1.1 and 0.51 per 100,000 for incidence and mortality, respectively. ASR for both incidence and mortality were approximately four times higher in men and varied greatly across geographical regions and countries within the same region. Higher incidence was estimated in Europe, North-America, Australia, and New Zealand. Mortality was the highest in Central-East Europe, Western Europe, Melanesia, South-Central Asia, and the Caribbean. South-Central Asia, most African areas, and Central America exhibited the lowest IMR values, whereas North-America, Australia, New Zealand, and North-Europe had the highest. CONCLUSIONS: The marked geographical and gender variability in OPC incidence and mortality is likely to reflect the distribution of risk factors and the diverse prevalence of HPV-negative and HPV-positive cases. IMPACT: Findings are likely to drive future research, support the development of targeted strategies to counteract disease burden, establish priorities for prevention and treatment programs, and address inequality in access to services.

Major Amputation In Non-Healing Ulcers: Outcomes and Economic Issues. Data from a Cohort of Patients with Diabetic Foot Ulcers.

Background: Foot ulcers have a relevant economic impact on Health Care Systems and the cost-effectivenesseffectiveness of options is not clear. The aim of this study was the assessment of costs for ulcers treatment after 6, 12, and 18 months of follow-up, compared to those for major amputation. Methods: A retrospective study was carried out on 196 types 2 diabetic patients with foot ulcers. The principal endpoints were 1) the proportion of recovered patients among those with ulcers not healed after 6 and 12 months; 2) the assessment of direct costs for treatment of ulcers 6, 12, and 18 months of follow-up, as compared to the cost of major amputation. The economic evaluation was performed considering the perspective of the local health system. Results: Out of 196 patients, 85(46.2%), 131(71.6%), and 140(85.9%) healed within 6, 12, and 18 months, respectively. The average health cost during the 18-month follow-up was 5402€ per patient. We calculated hypothetical costs for three different scenarios, in which patients who did not heal within 6 months underwent a major amputation at 6, 1,2, or 18 months. Costs for the standard of care for all these scenarios (6,094, 7,256, and 7649€ for 6, 12, or 18 months, respectively) were significantly lower than that for major amputations (21,065€). Conclusions: A conservative approach appears more convenient than major amputations in ulcers not healing after 6 months, irrespective of the estimated risk of individual patients.

Minimally invasive distal pancreatectomy: a case-matched cost-analysis between robot-assisted surgery and direct manual laparoscopy.

BACKGROUND: Few studies have reported a structured cost analysis of robotic distal pancreatectomy (RDP), and none have compared the relative costs between the robotic-assisted surgery (RAS) and the direct manual laparoscopy (DML) in this setting. The aim of the present study is to address this issue by comparing surgical outcomes and costs of RDP and laparoscopic distal pancreatectomies (LDP). METHODS: Eighty-eight RDP and 47 LDP performed between January 2008 and January 2020 were retrospectively analyzed. Three comparable groups of 35 patients each (Si-RDP-group, Xi-RDP group, LDP-group) were obtained matching 1:1 the RDP-groups with the LDP-group. Overall costs, including overall variable costs (OVC) and fixed costs were compared using generalized linear regression model adjusting for covariates. RESULTS: The conversion rate was significantly lower in the Si-RDP-group and Xi-RDP-group: 2.9% and 0%, respectively, versus 14.3% in the LDP-group (p = 0.045). Although not statistically significant, the mean operative time was lower in Xi-RDP-group: 226 min versus 262 min for Si-RDP-group and 247 min for LDP-group. The overall post-operative complications rate and the length of hospital stay (LOS) were not significantly different between the three groups. In LDP-group, the LOS of converted cases was significantly longer: 15.6 versus 9.8 days (p = 0.039). Overall costs of LDP-group were significantly lower than RDP-groups, (p < 0.001). At multivariate analysis OVC resulted no longer statistically significantly different between LDP-group and Xi-RDP-group (p = 0.099), and between LDP-group and the RDP-groups when the spleen preservation was indicated (p = 0.115 and p = 0.261 for Si-RDP-group and Xi-RDP-group, respectively). CONCLUSIONS: RAS is more expensive than DML for DP because of higher acquisition and maintenance costs. The flattening of these differences considering only the variable costs, in a high-volume multidisciplinary center for RAS, suggests a possible optimization of the costs in this setting. RAS might be particularly indicated for minimally invasive DP when the spleen preservation is scheduled.

Robot-assisted pancreatoduodenectomy with the da Vinci Xi: can the costs of advanced technology be offset by clinical advantages? A case-matched cost analysis versus open approach.

BACKGROUND: Robot-assisted pancreatoduodenectomy (RPD) has shown some advantages over open pancreatoduodenectomy (OPD) but few studies have reported a cost analysis between the two techniques. We conducted a structured cost-analysis comparing pancreatoduodenectomy performed with the use of the da Vinci Xi, and the traditional open approach, and considering healthcare direct costs associated with the intervention and the short-term post-operative course. MATERIALS AND METHODS: Twenty RPD and 194 OPD performed between January 2011 and December 2020 by the same operator at our high-volume multidisciplinary center for robot-assisted surgery and for pancreatic surgery, were retrospectively analyzed. Two comparable groups of 20 patients (Xi-RPD-group) and 40 patients (OPD-group) were obtained matching 1:2 the RPD-group with the OPD-group. Perioperative data and overall costs, including overall variable costs (OVCs) and fixed costs, were compared. RESULTS: No difference was reported in mean operative time: 428 min for Xi-RPD-group versus 404 min for OPD, p = 0.212. The median overall length of hospital stay was significantly lower in the Xi-RPD-group: 10 days versus 16 days, p = 0.001. In the Xi-RPD-group, consumable costs were significantly higher (€6149.2 versus €1267.4, p < 0.001), while hospital stay costs were significantly lower: €5231.6 versus €8180 (p = 0.001). No significant differences were found in terms of OVCs: €13,483.4 in Xi-RPD-group versus €11,879.8 in OPD-group (p = 0.076). CONCLUSIONS: Robot-assisted surgery is more expensive because of higher acquisition and maintenance costs. However, although RPD is associated to higher material costs, the advantages of the robotic system associated to lower hospital stay costs and the absence of difference in terms of personnel costs thanks to the similar operative time with respect to OPD, make the OVCs of the two techniques no longer different. Hence, the higher costs of advanced technology can be partially compensated by clinical advantages, particularly within a high-volume multidisciplinary center for both robot-assisted and pancreatic surgery. These preliminary data need confirmation by further studies.

Cost-effectiveness of treatment optimisation with biomarkers for immunotherapy in solid tumours: a systematic review protocol.

INTRODUCTION: The combination of biomarkers and drugs is the subject of growing interest both from regulators, physicians and companies. This study protocol of a systematic review is aimed to describe available literature evidences about the cost-effectiveness, cost-utility or net-monetary benefit of the use of biomarkers in solid tumour as tools for customising immunotherapy to identify what further research needs. METHODS AND ANALYSIS: A systematic review of the literature will be carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. PubMed and Embase will be queried from June 2010 to June 2021. The PICOS model will be applied: target population (P) will be patients with solid tumours treated with immune checkpoint inhibitors (ICIs); the interventions (I) will be test of the immune checkpoint predictive biomarkers; the comparator (C) will be any other targeted or non-targeted therapy; outcomes (O) evaluated will be health economic and clinical implications assessed in terms of incremental cost-effectiveness ratio, net health benefit, net monetary benefit, life years gained, quality of life, etc; study (S) considered will be economic evaluations reporting cost-effectiveness analysis, cost-utility analysis, net-monetary benefit. The quality of the evidence will be graded according to Grading of Recommendations Assessment, Development and Evaluation. ETHICS AND DISSEMINATION: This systematic review will assess the cost-effectiveness implications of using biomarkers in the immunotherapy with ICIs, which may help to understand whether this approach is widespread in real clinical practice. This research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in a related peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020201549.

New Perspective to Improve Care of Patients with Infected Diabetic Foot Ulcer: Early Economic Impact of the Use of Photodynamic Therapy with RLP068 (Based) System.

OBJECTIVE: To perform an early economic evaluation of a system based on photodynamic advanced adjuvant therapy with photosensitizer RLP068/CI to facilitate the healing process of foot/leg skin lesions/ulcers with an excellent safety profile. DESIGN: An early short-term (10 weeks) cost-effectiveness and a budget impact analysis (over 5 years) comparing photodynamic therapy with photosensitizer RLP068/CI based (PDT-RLP068) system added to Standard of Care (SoC) vs SoC alone. SETTING: The Italian National Healthcare System perspective considering both the outpatient and the day-hospital regimen. PARTICIPANTS: Hypothetical patients with diabetic foot infection (DFI) grades I/IIB. INTERVENTIONS: The PDT-RLP068 system as an add-on to Standard of Care (SoC) vs SoC alone as the first-line treatment for the management of DFIs. MAIN OUTCOMES: Days within which the clinical target was achieved and direct health costs for patients' management. RESULTS: Additional costs generated by the use of the PDT-RLP068 system progressively decreased as time to reach the target induced by the novel system decreased. In the outpatient regimen, when time to reach clinical target decreased in the range 7-28 days, ICERs varied from about 1€ to 70€ for each additional day gained with clinical target achieved. The system was dominant when halving time to reach the target in the outpatient regimen and even for modest reduction of time in day-hospital regimen. In terms of budget impact, when considering day-hospital regimen, if the PDT-RLP068 based system allowed a shortened duration to reach the clinical target of between 7-28 days, BI was 8,100,000€ to 700,000€, with saving less than 2,000,000€ with 50% reduction of time. Considering the inpatient setting, the use of the PDT-RLP068 system would result in saving even with the modest impact on the time needed to activate the healing process. CONCLUSION: The early economic evaluation performed suggested that, if the claimed effectiveness of the technology demonstrated in case reports and in preliminary clinical studies can be confirmed in larger population studies, and allowing for shortening of the time needed to activate the healing process, the PDT-RLP068 system could offer the chance to improve care for DFI patients without compromising the sustainability of the system.

Cost-Effectiveness of Direct Non-Vitamin K Oral Anticoagulants Versus Vitamin K Antagonists for the Management of Patients with Non-Valvular Atrial Fibrillation Based on Available "Real-World" Evidence: The Italian National Health System Perspective.

BACKGROUND AND OBJECTIVE: The increasing availability of real-world evidence (RWE) about safety and effectiveness of direct non-vitamin K oral anticoagulants (DOACs) for the management of atrial fibrillation (AF) offers the opportunity to better understand the clinical and economic implications of DOACs versus vitamin K antagonists (VKAs). The objective of this study was to compare the economic implications of DOACs and VKAs using data from real-world evidence in patients with AF. METHODS: A Markov model simulating the lifetime course of patients diagnosed with non-valvular AF was used to evaluate the cost-effectiveness of DOACs (i.e., rivaroxaban, dabigatran and apixaban) versus VKAs from the Italian National Health System (INHS) perspective. The model was made up of data from the literature and a meta-analysis of RWE on the incidence of stroke/systemic embolism (SE), major bleeding (MB), intracranial haemorrhage (ICH) and all-cause mortality (ACM); direct costs included drug costs, costs for drug monitoring, and management of events from official national lists. One-way and probabilistic sensitivity analyses (PSA) were used to assess the robustness of the results. RESULTS: Results from the meta-analysis showed that apixaban had a high probability of being the most effective for stroke/SE, MB and ACM. Despite their higher acquisition costs, the cost-effectiveness analysis showed all DOACs involved a saving when compared with VKAs, with per-patient savings ranging between €4647 (rivaroxaban) to €6086 (apixaban). Moreover, all DOACs indicated a gain both in quality-adjusted life-years and life-years. According to PSA, findings related to apixaban were consistent, while for dabigatran and rivaroxaban PSA revealed a higher degree of uncertainty. CONCLUSIONS: The beneficial effect of DOACs on containing events showed in RWE had the potential to offset drug-related costs, thus improving the sustainability of treatment for non-valvular AF in daily clinical practice.

RarERN Path: a methodology towards the optimisation of patients' care pathways in rare and complex diseases developed within the European Reference Networks.

BACKGROUND: In 2017, the European Commission has launched the European Reference Networks (ERNs), virtual networks involving healthcare providers across Europe. The aim of the ERNs is to tackle complex and rare diseases and conditions that require highly specialized treatment and a concentration of knowledge and resources. The ERN on rare and complex connective tissue and musculoskeletal diseases (ERN ReCONNET) is one of the 24 ERNs approved that aims to improve the management of Rare and Complex Connective Tissue and Musculoskeletal Diseases. OBJECTIVE: The RarERN Path methodology aims to create a single reference organisational model for patients' care pathways which, if applied in different contexts, helps to ensure an improved, cost-effective and patient-centred equal care to rare and complex diseases. METHODS: Starting from existing standard methods for the creation and elaboration of patients' care pathways, a specific methodology was created in order to take advantage of the distinctive and peculiar characteristics of the ERNs. Specifically, the development of the RarERN Path methodology involved different stakeholders: health economists, clinicians and researchers expert in rare and complex diseases, communication experts, experts in patients' involvement and narrative medicine and policy-makers. RESULTS: The RarERN Path methodology foresees six consecutive phases, each with different and specific aims. Specifically, the six phases are represented by: Phase 1-mapping of existing patients' care pathways and patients' stories; Phase 2-design of an optimised common patients' care pathway; Phase 3-consensus on an optimised common patients' care pathway; Phase 4-key performance indicators definition; Phase 5-refinement; Phase 6-pilot phase (optional). CONCLUSION: The application of RarERN Path to the different disease-specific and geographical contexts would help to ensure an improved, cost-effective and patient-centred equal care to rare and complex diseases across Europe as well as a possible tangible action towards the integration of ERNs into the different European healthcare systems.

Correction to: Cost­effectiveness analysis of stand­alone or combined non­invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study.

In the Published article, the value in the abstract has been published incorrectly. The correct abstract section is as follows.

Cost-effectiveness analysis of stand-alone or combined non-invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study.

AIM: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study. METHODS AND RESULTS: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering "no-imaging" as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from - 969€/cd for CMR-CTCA to - 1490€/cd for CTCA-PET, - 3092€/cd for CTCA-SPECT and - 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure. CONCLUSION: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization.

Structured cost analysis of robotic TME resection for rectal cancer: a comparison between the da Vinci Si and Xi in a single surgeon's experience.

BACKGROUND: Robotic-assisted surgery by the da Vinci Si appears to benefit rectal cancer surgery in selected patients, but still has some limitations, one of which is its high costs. Preliminary studies have indicated that the use of the new da Vinci Xi provides some added advantages, but their impact on cost is unknown. The aim of the present study is to compare surgical outcomes and costs of rectal cancer resection by the two platforms, in a single surgeon's experience. METHODS: From April 2010 to April 2017, 90 robotic rectal resections were performed, with either the da Vinci Si (Si-RobTME) or the da Vinci Xi (Xi-RobTME). Based on CUSUM analysis, two comparable groups of 40 consecutive Si-RobTME and 40 consecutive Xi-RobTME were obtained from the prospectively collected database and used for the present retrospective comparative study. Data costs were analysed based on the level of experience on the proficiency-gain curve (p-g curve) by the surgeon with each platform. RESULTS: In both groups, two homogeneous phases of the p-g curve were identified: Si1 and Xi1: cases 1-19, Si2 and Xi2: cases 20-40. A significantly higher number of full RAS operations were achieved in the Xi-RobTME group (p < 0.001). A statistically significant reduction in operating time (OT) during Si2 and Xi2 phase was observed (p < 0.001), accompanied by reduced overall variable costs (OVC), personnel costs (PC) and consumable costs (CC) (p < 0.001). All costs were lower in the Xi2 phase compared to Si2 phase: OT 265 versus 290 min (p = 0.052); OVC 7983 versus 10231.9 (p = 0.009); PC 1151.6 versus 1260.2 (p = 0.052), CC 3464.4 versus 3869.7 (p < 0.001). CONCLUSIONS: Our experience confirms a significant reduction of costs with increasing surgeon's experience with both platforms. However, the economic gain was higher with the Xi with shorter OT, reduced PC and CC, in addition to a significantly larger number of cases performed by the fully robotic approach.

Rare diseases under different levels of economic analysis: current activities, challenges and perspectives.

Rare diseases imply clinical and economic burden as well as a significant challenge for health systems. One relevant objective of the activities planned within the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) is to address the economic dimensions of rare diseases to identify, develop and suggest strategies to improve research and patients' access to orphan drugs (ODs) and highly specialised health technologies. This paper presents a preliminary review of the existing policies on rare diseases in the countries of the Network members. It also introduces and discusses the theme of how to perform health economic evaluations of rare diseases and of existing or new treatments for rare diseases. To obtain a preliminary overview aiming at defining the state of the art of rare diseases policies and initiatives in ERN ReCONNET countries, we collected and analysed the rare diseases national plans of all the eight countries of the ERN ReCONNET participants. The preliminary overview that has been performed showed that in all the ERN ReCONNET countries are in place national plans for rare diseases; however, heterogeneity exists in the reimbursement of ODs, direct provision by the healthcare system, involvement of patients' associations in decision making and implementation of clinical practice guidelines.

Budget impact analysis of the use of extended half-life recombinant factor VIII (efmoroctocog alfa) for the treatment of congenital haemophilia a: the Italian National Health System perspective.

BACKGROUND: Congenital haemophilia A (HA) is a rare, inherited, life-long bleeding disorder characterised by prolonged or spontaneous bleeding due to the lack of clotting factor VIII (FVIII) in the body. Treatment for HA involves FVIII replacement therapy and poses great economic burden to National Health Systems and to society. Availability of novel products as extended half-life clotting factor products might change treatment approches and their economic evaluation is essential for an informed treatment choice. Accordingly the objective of the present work is to analyse the economic impact of using efmoroctocog alfa (recombinant factor VIII-Fc fusion protein, rFVIIIFc) for the treatment of children and adults with severe congenital haemophilia A (HA). METHODS: A budget impact analysis was performed to estimate the economic impact of the introduction of rFVIIIFc in the market-mix of products for the treatment of HA. The analysis condidered a 3-year time horizon and the Italian National Health System (INHS) perspective. The model estimated drug costs associated with the treatment of HA in the current scenario - representing the marketplace forecast for the time period of interest assuming that rFVIIFc is not introduced - and a new scenario, assuming that rFVIIIFc is available in the market. The size of the target population was calculated using epidemiological national data. Univariate one-way sensitivity analyses and scenario analyses were performed. RESULTS: Overall 3-year costs of treating the HA population in the current scenario were 555,277,691 Euro for the INHS. With the introduction of rFVIIIFc, the costs were reduced to 541,897,466 Euro suggesting potential savings to the INHS of 13,380,255 Euro. Results were consistent at variation of most of the model's parameters; only in case of lower dosage of conventional products and higher dosage of rFVIIIFc, costs for the INHS increased, in both cases, of about 20 million Euro. CONCLUSIONS: The use of rFVIIIFc for the treatment of HA has been recently approved by the Italian Medicines Agency (AIFA) and this is the first study estimating the financial impact of this new therapeutic alternative in the Italian context. The analysis suggests that rFVIIIFc use does not result in higher expenditure for the INHS.

Cost-consequence analysis of sitagliptin versus sulfonylureas as add-on therapy for the treatment of diabetic patients in Italy.

OBJECTIVE: Diabetes mellitus is a chronic disease related to a significant impact in both epidemiologic and economic terms. In Italy, around 3.6 million people are affected by diabetes and this number is expected to increase significantly in the next few years. As recommended by current national and international guidelines, metformin (Met) is prescribed as first-line pharmacological treatment, and many pharmacological alternatives are available for patients uncontrolled with Met monotherapy. Despite the availability of many innovative oral antidiabetic drugs (OADs), such as dipeptidyl peptidase 4 inhibitors (DPP4-i) and its first-in-class sitagliptin (SITA), which entered the Italian market in the last 10 years, their usage is consistently lower than traditional drugs such as sulfonylureas (SUs). In fact, due to higher acquisition costs, the prescription of innovative OADs in Italy is restricted to specialist, resulting in a prominent usage of traditional OAD that can be prescribed also by general practitioners (GPs). A cost consequence analysis (CCA) was performed in order to compare SITA with SU, as second-line therapy in add-on to Met, in terms of costs and related clinical events over 36 months. METHODS: A CCA was conducted on a hypothetical cohort of 100,000 type 2 diabetes mellitus (T2DM) patients uncontrolled with Met monotherapy, from both the Italian National Health Service (INHS) and societal perspective. Therefore, both direct (drugs, self-monitoring, hypoglycemia, major cardiovascular events [MACEs], and switch to insulin) and indirect costs (expressed in terms of productivity losses) were evaluated. Clinical and economic data were collected through Italian national tariffs, literature, and experts' opinions. Three expert clinicians finally validated data inputs. To assess robustness of base case results, a one-way sensitivity analysis (OWSA) and a conservative scenario analysis - excluding MACEs - were carried out. RESULTS: In the base case analysis, the higher drug costs related to SITA were offset by other management costs (ie, lower use of devices for glycemia self-monitoring, lower incidence of hypoglycemia and MACE, and delay to insulin switch). As a result, the economic evaluation showed that, compared to SU, SITA was cost saving from both societal (-€61,217,723) and INHS (-€51,846,442) perspectives over 3 years as add-on to Met. The base case results were also confirmed by the scenario analysis and by the OWSA performed on the key parameters. The adoption of SITA, in a cohort of 100,000 diabetes patients, would avoid 26,882 non-severe hypoglycemic events, 6,528 severe hypoglycemic events, and 1,562 MACEs. CONCLUSION: This analysis suggests that, compared to SU, SITA could be a sustainable and cost-saving alternative for the management of T2DM patients uncontrolled with Met monotherapy from both clinical and economic perspectives.

BUDGET IMPACT ANALYSIS OF BELIMUMAB IN TREATING SYSTEMIC LUPUS ERYTHEMATOSUS.

OBJECTIVES: The study evaluates the costs of systemic lupus erythematosus (SLE) and the budget impact due to the introduction of belimumab in the Italian setting. METHODS: Adaptation to the Italian setting of a budget impact model with a time horizon of 4 years (year 0 without belimumab, years 1-3 with belimumab) to compare treatment, administration, and clinical monitoring costs of standard therapy and of the alternative scenario in which belimumab is administered in addition to the standard therapy to the subgroup of patients selected according to the label approved by the European Medicines Agency. The model takes also into account the costs of flares. RESULTS: Over 3 years, belimumab is able to prevent cumulatively 1,111 severe flares and 3,631 nonsevere flares with a total saving for the Italian National Health System (NHS) of approximately €6.2 million. Budget impact ranges from €4.4 million in the first year to €20.3 million in the third year. CONCLUSIONS: The decrease in the number of flare partially counterbalances the costs of the new technology (impact attenuation of approximately 16 percent). These data elucidate the importance to control and monitor the disease progression and to prevent exacerbations, which are the major causes of the increase in costs paid by the NHS and by the society. The financial impact could be replicate on a regional basis, to inform local decision makers. Further developments are possible as the model does not consider the additional clinical and economic benefits of reduced damage accrual and slowed disease progression.