The PICOTS-ComTeC Framework for Defining Digital Health Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: Digital health definitions are abundant, but often lack clarity and precision. We aimed to develop a minimum information framework to define patient-facing digital health interventions (DHIs) for outcomes research. METHODS: Definitions of digital-health-related terms (DHTs) were systematically reviewed, followed by a content analysis using frameworks, including PICOTS (population, intervention, comparator, outcome, timing, and setting), Shannon-Weaver Model of Communication, Agency for Healthcare Research and Quality Measures, and the World Health Organization's Classification of Digital Health Interventions. Subsequently, we conducted an online Delphi study to establish a minimum information framework, which was pilot tested by 5 experts using hypothetical examples. RESULTS: After screening 2610 records and 545 full-text articles, we identified 101 unique definitions of 67 secondary DHTs in 76 articles, resulting in 95 different patterns of concepts among the definitions. World Health Organization system (84.5%), message (75.7%), intervention (58.3%), and technology (52.4%) were the most frequently covered concepts. For the Delphi survey, we invited 47 members of the ISPOR Digital Health Special Interest Group, 18 of whom became the Delphi panel. The first, second, and third survey rounds were completed by 18, 11, and 10 respondents, respectively. After consolidating results, the PICOTS-ComTeC acronym emerged, involving 9 domains (population, intervention, comparator, outcome, timing, setting, communication, technology, and context) and 32 optional subcategories. CONCLUSIONS: Patient-facing DHIs can be specified using PICOTS-ComTeC that facilitates identification of appropriate interventions and comparators for a given decision. PICOTS-ComTeC is a flexible and versatile tool, intended to assist authors in designing and reporting primary studies and evidence syntheses, yielding actionable results for clinicians and other decision makers.

Disruptive technologies in health care disenchanted: a systematic review of concepts and examples.

OBJECTIVES: To clarify the concept of disruptive technologies in health care, provide examples and consider implications of potentially disruptive technologies for health technology assessment (HTA). METHODS: We conducted a systematic review of conceptual and empirical papers on healthcare technologies that are described as "disruptive." We searched MEDLINE and Embase from 2013 to April 2019 (updated in December 2021). Data extraction was done in duplicate by pairs of reviewers utilizing a data extraction form. A qualitative data analysis was undertaken based on an analytic framework for analysis of the concept and examples. Key arguments and a number of potential predictors of disruptive technologies were derived and implications for HTA organizations were discussed. RESULTS: Of 4,107 records, 28 were included in the review. Most of the papers included conceptual discussions and business models for disruptive technologies; only few papers presented empirical evidence. The majority of the evidence is related to the US healthcare system. Key arguments for describing a technology as disruptive include improvement of outcomes for patients, improved access to health care, reduction of costs and better affordability, shift in responsibilities between providers, and change in the organization of health care. A number of possible predictors for disruption were identified to distinguish these from "sustaining" innovations. CONCLUSIONS: Since truly disruptive technologies could radically change technology uptake and may modify provision of care patterns or treatment paths, they require a thorough evaluation of the consequences of using these technologies, including economic and organizational impact assessment and careful monitoring.

Standardized reporting for rapid relative effectiveness assessments of pharmaceuticals.

OBJECTIVES: Many European countries perform rapid assessments of the relative effectiveness (RE) of pharmaceuticals as part of the reimbursement decision making process. Increased sharing of information on RE across countries may save costs and reduce duplication of work. The objective of this article is to describe the development of a tool for rapid assessment of RE of new pharmaceuticals that enter the market, the HTA Core Model® for Rapid Relative Effectiveness Assessment (REA) of Pharmaceuticals. METHODS: Eighteen member organisations of the European Network of Health Technology Assessment (EUnetHTA) participated in the development of the model. Different versions of the model were developed and piloted in this collaboration and adjusted accordingly based on feedback on the content and feasibility of the model. RESULTS: The final model deviates from the traditional HTA Core Model® used for assessing other types of technologies. This is due to the limited scope (strong focus on RE), the timing of the assessment (just after market authorisation), and strict timelines (e.g. 90 days) required for performing the assessment. The number of domains and assessment elements was limited and it was decided that the primary information sources should preferably be a submission file provided by the marketing authorisation holder and the European Public Assessment Report. CONCLUSIONS: The HTA Core Model® for Rapid REA (version 3.0) was developed to produce standardised transparent RE information of pharmaceuticals. Further piloting can provide input for possible improvements, such as further refining the assessment elements and new methodological guidance on relevant areas.

Piloting international production of rapid relative effectiveness assessments of pharmaceuticals.

BACKGROUND: This article describes the lessons learned from an international pilot assessment using the first version of the HTA Core Model® and Guidelines for rapid Relative Effectiveness Assessment (REA) of pharmaceuticals based on input from three different perspectives: the assessors, the users (health technology assessment organisations) and the marketing authorisation holder. METHODS: A pilot assessment was performed of pazopanib for the treatment of advanced or metastatic renal cell carcinoma for which 54 individuals from 22 EUnetHTA member organisations from 16 European countries gave their contribution. The work was divided in eight domain teams. Subsequently, results of these domain teams were synthesised in one pilot report. Feedback on the outcomes of the pilot was gathered throughout the project and through structured surveys. RESULTS: The first version of the assessment was produced in six months and consisted of 55 question and answer pairs, 8 domain reports and a synthesis section that combined the results from the different domains. The organisation of the pilot required intense coordination. Main points of criticism on the assessment were the lengthiness of the document and overlap of information throughout the assessment. CONCLUSIONS: A reduction in the number of authoring organisations and individuals participating is necessary to avoid information overlap and increase efficiency in undertaking the assessment. Involving several organisations (e.g. five) in an in-depth review could still ensure the benefit of broad participation from various countries. The focus of a rapid REA should be on the first four domains of the Model.

Overcoming Barriers in Hospital-Based Health Technology Assessment (HB-HTA): International Expert Panel Consensus.

The purpose of this article is to investigate the common facilitators and barriers associated with the implementation of hospital-based health technology assessment (HB-HTA) across diverse hospital settings in seven countries. Through a two-round Delphi study, insights were gathered from a panel of 15 HTA specialists from France, Hungary, Italy, Kazakhstan, Poland, Switzerland, and Ukraine. Experts initially conducted a comprehensive review of the HB-HTA implementation in their respective countries, identifying the barriers and facilitators through descriptive analysis. Subsequently, panel experts ranked these identified barriers and facilitators on a seven-point Likert scale. A median agreement score ≥ 6 and interquartile range (IQR) ≤ 1 was accepted as reaching a consensus. Out of the 12 statements categorized as external and internal barriers and facilitators, the expert panel reached consensus on six statements (two barriers and four facilitators). The external barrier, which achieved consensus, was the lack of the formal recognition of the role of HB-HTA in national or regional legislations. The internal barrier reaching consensus was the limited availability of human resources dedicated to HB-HTA. This qualitative study indicates that HB-HTA still has progress to make before being formally accepted and integrated across most countries, although by building on the facilitating factors we identified there may be an opportunity for the implementation of internationally developed strategies to strengthen HB-HTA practices.

Access and reimbursement pathways for digital health solutions and in vitro diagnostic devices: Current scenario and challenges.

Objectives: Digital therapeutics (DTx) are innovative solutions that use meaningful data to provide evidence-based decisions for the prevention, treatment, and management of diseases. Particular attention is paid to software-based in vitro diagnostics (IVDs). With this point of view, a strong connection between DTx and IVDs is observed. Methods: We investigated the current regulatory scenarios and reimbursement approaches adopted for DTx and IVDs. The initial assumption was that countries apply different regulations for the access to the market and adopt different reimbursement systems for both DTx and IVDs. The analysis was limited to the US, European countries (Germany, France, and UK), and Australia due to maturity in digital health product adoption and regulatory processes, and recent regulations related to IVDs. The final aim was to provide a general comparative overview and identify those aspects that should be better addressed to support the adoption and commercialization of DTx and IVDs. Results: Many countries regulate DTx as medical devices or software integrated with a medical device, and some have a more specific pathway than others. Australia has more specific regulations classifying software used in IVD. Some EU countries are adopting similar processes to the Digital Health Applications (DiGA) under Germany's Digitale-Versorgung Gesetz (DVG) law, which deems DTx eligible for reimbursement during the fast access pathway. France is working on a fast-track system to make DTx available to patients and reimbursable by the public system. The US retains some coverage through private insurance, federal and state programs like Medicaid and Veterans Affairs, and out-of-pocket spending. The updated Medical Devices Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR) in the EU includes a classification system specifying how software integrated with medical devices, and IVDs specifically must be regulated. Conclusion: The outlook for DTx and IVDs is changing as they are becoming more technologically advanced, and some countries are adapting their device classifications depending on specific features. Our analysis showed the complexity of the issue demonstrating how fragmented are regulatory systems for DTx and IVDs. Differences emerged in terms of definitions, terminology, requested evidence, payment approaches and the overall reimbursement landscape. The complexity is expected to have a direct impact on the commercialization of and access to DTx and IVDs. In this scenario, willingness to pay of different stakeholders is a key theme.

Scoping Meta-Review of Methods Used to Assess Artificial Intelligence-Based Medical Devices for Heart Failure.

Artificial intelligence and machine learning (AI/ML) are playing increasingly important roles, permeating the field of medical devices (MDs). This rapid progress has not yet been matched by the Health Technology Assessment (HTA) process, which still needs to define a common methodology for assessing AI/ML-based MDs. To collect existing evidence from the literature about the methods used to assess AI-based MDs, with a specific focus on those used for the management of heart failure (HF), the International Federation of Medical and Biological Engineering (IFMBE) conducted a scoping meta-review. This manuscript presents the results of this search, which covered the period from January 1974 to October 2022. After careful independent screening, 21 reviews, mainly conducted in North America and Europe, were retained and included. Among the findings were that deep learning is the most commonly utilised method and that electronic health records and registries are among the most prevalent sources of data for AI/ML algorithms. Out of the 21 included reviews, 19 focused on risk prediction and/or the early diagnosis of HF. Furthermore, 10 reviews provided evidence of the impact on the incidence/progression of HF, and 13 on the length of stay. From an HTA perspective, the main areas requiring improvement are the quality assessment of studies on AI/ML (included in 11 out of 21 reviews) and their data sources, as well as the definition of the criteria used to assess the selection of the most appropriate AI/ML algorithm.

Personalized Predictive Hemodynamic Management for Gynecologic Oncologic Surgery: Feasibility of Cost-Benefit Derivatives of Digital Medical Devices.

BACKGROUND: Intraoperative hypotension is associated with increased perioperative complications, hospital length of stay (LOS) and healthcare expenditure in gynecologic surgery. We tested the hypothesis that the adoption of a machine learning-based warning algorithm (hypotension prediction index-HPI) might yield an economic advantage, with a reduction in adverse outcomes that outweighs the costs for its implementation as a medical device. METHODS: A retrospective-matched cohort cost-benefit Italian study in gynecologic surgery was conducted. Sixty-six female patients treated with standard goal-directed therapy (GDT) were matched in a 2:1 ratio with thirty-three patients treated with HPI based on ASA status, diagnosis, procedure, surgical duration and age. RESULTS: The most relevant contributor to medical costs was operating room occupation (46%), followed by hospital stay (30%) and medical devices (15%). Patients in the HPI group had EURO 300 greater outlay for medical devices without major differences in total costs (GDT 5425 (3505, 8127), HPI 5227 (4201, 7023) p = 0.697). A pre-specified subgroup analysis of 50% of patients undergoing laparotomic surgery showed similar medical device costs and total costs, with a non-significant saving of EUR 1000 in the HPI group (GDT 8005 (5961, 9679), HPI 7023 (5227, 11,438), p = 0.945). The hospital LOS and intensive care unit stay were similar in the cohorts and subgroups. CONCLUSIONS: Implementation of HPI is associated with a scenario of cost neutrality, with possible economic advantage in high-risk settings.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Value assessment of medicinal products by the Italian Medicines Agency (AIFA) and French National Authority for Health (HAS): Similarities and discrepancies.

The evaluation of pharmaceutical innovation and therapeutic value is an increasingly complex exercise for which different approaches are adopted at the national level, despite the need for standardisation of processes and harmonisation of public health decisions. The objective of our analysis was to compare the approaches of the AIFA (Agenzia Italiana del Farmaco) and the HAS (Haute Autorité de Santé) in assessing the same medicinal products. In Italy, the 1525/2017 AIFA Deliberation introduces a transparent scheme for the evaluation of innovative status (innovative, conditional, not innovative) based on the therapeutic added value (TAV), therapeutic need, and quality of evidence. In contrast, in France, the HAS makes judgements using the effective clinical benefit (Service Médical Rendu) and improvement of effective clinical benefit (Amélioration du Service Médical Rendu, ASMR). This analysis focused on medicinal products evaluated both by the AIFA and by the HAS from July 2017 to September 2021. Similarities between AIFA and HAS evaluations were investigated in terms of the TAV, recognition of innovativeness, and the ASMR. Both total and partial agreements were considered relevant. Therefore, raw agreement, Cohen's kappa (weighted and unweighted), and Bangdiwala's B-statistic were estimated. A total of 102 medicinal products were included in this study. Out of these, 38 (37.2%) were orphan drugs, while 56 (54.9%) had a clinical indication for the treatment of cancer. The AIFA and HAS reached a higher level of agreement on the innovativeness status compared with the TAV. A moderate total agreement emerged in the recognition of innovativeness (k = 0.463, p-value ≤0.0001), and partial agreement was substantial (equal weight k = 0.547, squared k = 0.638), while a lack of agreement resulted in a comparison of the TAV according to the AIFA and the ASMR recognised by the HAS. Indeed, whereas the AIFA determined the TAV to be important, the HAS considered it to be moderate. In addition, whereas the AIFA identified a bias towards a moderate TAV, the HAS identified a bias towards a minor ASMR. A higher level of agreement was reached, both on the TAV and on innovative status, for less critical medical products (non-cancer-related, or non-orphan, or with a standard European Medicines Agency approval). These results underline the importance of implementing European procedures that are more broadly aligned in terms of value definition criteria.

New first-line immunotherapy-based combinations for metastatic renal cell carcinoma: A systematic review and network meta-analysis.

Several first-line immune-checkpoints inhibitors (ICI) based combinations have been studied in metastatic renal cell carcinoma (mRCC) without any direct comparison between the regimens. The objective of this systematic review and network meta-analysis was to provide the most updated evidence about the preferred first line ICI-based regimen for mRCC. We searched various databases, including PubMed, Web of Science and Scopus and the major conference proceedings (ASCO, ESMO). Eligible studies were randomized trial, published before June 2021 that evaluated first-line, ICI-based combinations compared with the standard of care in mRCC. Screening was performed independently by two investigators. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by Bayesian network meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate, complete response and adverse events. Six trials with 5478 patients comparing 7 treatments were identified. Network meta-analysis showed that lenvatinib plus pembrolizumab had the highest probability to be the best treatment in terms of OS (surface under the cumulative ranking (SUCRA) 80.7%) and PFS (SUCRA 99.6%), while in sarcomatoid patients, nivolumab plus cabozantinib had the highest rank in terms of survival outcomes (SUCRA 85.8% and SUCRA 77.3%, respectively). Although we established a ranking among new first-line mRCC treatment combinations, the absence of direct comparisons between the multiple treatment options represents a major hurdle in establishing optimal therapeutic sequences. Our results could represent a starting point for head-to-head trials between the most promising combinations.

Road Toward a New Model of Care for Idiopathic Pulmonary Fibrosis in the Lazio Region.

A timely, confirmed diagnosis of Idiopathic Pulmonary Fibrosis (IPF) has a significant impact on the evolution of the disease. The current model of care in the Lazio region (in Italy) was assessed on the basis of real-world data provided by the four reference centers responsible for diagnosing and treating IPF. The 5-year, population-based, retrospective longitudinal study provided the data that is at the basis of the current proposal for a new clinical and therapeutic pathway (DTCP) and has been shared with regional decision makers. A DTCP must be defined and based on four pillars: GPs, pulmonologists, IPF centers, and telemedicine. Each must play a role within a sort of hub-and-spoke model. IPF centers remain the hubs, while spokes are identified in trained GPs and pulmonologists.

Costs of bloodstream infections caused by Escherichia coli and influence of extended-spectrum-beta-lactamase production and inadequate initial antibiotic therapy.

Escherichia coli is the leading cause of bloodstream infections (BSIs) caused by Gram-negative bacteria. The increasing prevalence of antibiotic-resistant E. coli strains, particularly those producing extended-spectrum ß-lactamases (ESBLs), increases the odds that empirically prescribed antimicrobial therapy for these infections will be inadequate, but the economic impact of this risk has not been fully evaluated. In the present retrospective 1-year analysis of 134 consecutive E. coli BSIs in our hospital, we explored the clinical and economic impacts of (i) inadequate initial antimicrobial treatment (IIAT) (i.e., empirical treatment with drugs to which the isolate had displayed in vitro resistance) of these infections and (ii) ESBL production by the bloodstream isolate. Cost data were obtained from the hospital accounting system. Compared with the 107 (79.8%) adequately treated patients, the 27 (20.1%) who received IIAT had a higher proportion of ESBL BSIs (74.0% versus 15.8%), longer (+6 days) and more costly (+EUR 4,322.00) post-BSI-onset hospital stays, and higher 21-day mortality rates (40.7% versus 5.6%). Compared with the 97 non-ESBL infections, the 37 (27.6%) ESBL BSIs were also associated with longer (+7 days) and more costly (+EUR 5,026.00) post-BSI-onset hospital stays and increased 21-day mortality (29.7% versus 6.1%). These findings confirm that the hospital costs and mortality associated with E. coli BSIs are significantly increased by ESBL production and by IIAT.

Impact of SARS-CoV-2 on Provided Healthcare. Evidence From the Emergency Phase in Italy.

The SARS-CoV-2 (COVID-19) pandemic led to an emergency scenario within all aspects of health care, determining reduction in resources for the treatment of other diseases. A literature review was conducted to identify published evidence, from 1 March to 1 June 2020, regarding the impact of COVID-19 on the care provided to patients affected by other diseases. The research is limited to the Italian NHS. The aim is to provide a snapshot of the COVID-19 impact on the NHS and collect useful elements to improve Italian response models. Data available for oncology and cardiology are reported. National surveys, retrospective analyses, and single-hospital evidence are available. We summarized evidence, keeping in mind the entire clinical pathway, from clinical need to access to care to outcomes. Since the beginning, the COVID-19 pandemic was associated with a reduced access to inpatient (-48% for IMA) and outpatient services, with a lower volume of elective surgical procedures (in oncology, from 3.8 to 2.6 median number of procedures/week). Telehealth may plays a key role in this, particularly in oncology. While, for cardiology, evidence on health outcome is already available, in terms of increased fatality rates (for STEMI: 13.7 vs. 4.1%). To better understand the impact of COVID-19 on the health of the population, a broader perspective should be taken. Reasons for reduced access to care must be investigated. Patients fears, misleading communication campaigns, re-arranged clinical pathways could had played a role. In addition, impact on other the status of other patients should be mitigated.

The use of "harmonic scalpel" versus "knot tying" for conventional "open" thyroidectomy: results of a prospective randomized study.

PURPOSE: We evaluated the safety and cost-effectiveness of the harmonic scalpel (HS) during conventional "open" thyroidectomy (CT). MATERIALS AND METHODS: Two hundred patients scheduled for conventional total thyroidectomy (TT) were included in the study and randomly assigned to TT with the use of HS (HS group) or with knot tying technique (KT group). RESULTS: Mean operative time was significantly shorter in the HS group (P < 0.001), as well as the total operative room occupation time (P < 0.001). The cost of the disposable materials is significantly higher in the HS group (420.1 +/- 23.2 vs 137.8 +/- 25.3 euros; P < 0.001). Conversely, drugs, personnel and operative room charges were significantly higher in KT group patients (P < 0.001). Overall, no significant difference was found between the two groups concerning the charges of the hospitalisation (P = NS). CONCLUSIONS: HS is a safe alternative to KT, allowing for a significant reduction of operative time without increasing complications rate and overall costs and probably better utilization of health resources.

Budget impact of implementing platelet pathogen reduction into the Italian blood transfusion system.

BACKGROUND: Despite improvements in blood donor selection and screening procedures, transfusion recipients can still develop complications related to infections by known and emerging pathogens. Pathogen reduction technologies (PRT) have been developed to reduce such risks. The present study, developed whithin a wider health technology assessment (HTA) process, was undertaken to estimate the costs of the continuing increase in the use of platelet PRT in Italy. MATERIALS AND METHODS: A multidisciplinary team was established to perform the HTA and conduct a budget impact analysis. Quantitative data on platelet use were derived from the 2015 national blood transfusion report and from the Italian Platelets Transfusion Assessment Study (IPTAS). The current national fee of 60 Euro per platelet PRT procedure was used to quantify the costs to the Italian National Health Service (INHS). The analysis adopts a 3-year time-frame. In order to identify the impact on budget we compared a scenario representing an increased use of PRT platelets over time with a control scenario in which standard platelets are used. RESULTS: Progressive implementation of PRT for 20%, 40% and 66% of annual adult platelet doses could generate an increase in annual costs for the INHS amounting to approximately 7, 14 and 23 million Euros, respectively. Use of kits and devices suitable for the treatment of multiple adult platelet doses in one PRT procedure could lower costs. DISCUSSION: In order to fully evaluate the societal perspective of implementing platelet PRT, the increase in costs must be balanced against the expected benefits (prevention of transfusion-transmissible infections, white cell inactivation, extension of platelet storage, discontinuation of pathogen detection testing). Further studies based on actual numbers of platelet transfusion complications and their societal cost at a local level are needed to see the full cost to benefit ratio of platelet PRT implementation in Italy, and to promote equal treatment for all citizens.

The impact of stroke in Italy: first step for a National Burden of Disease Study.

PURPOSE: To calculate the impact of stroke in Italy in 1998, expressed in terms of disability adjusted life years (DALYs) according to the WHO Global Burden of Disease (GBD) Study. METHOD: The data on first-ever stroke incidence (FES), remission rate and case fatality derived from the health information system and a research on post-FES disability of the Friuli Venezia-Giulia (FVG) Region, were used to compute the years of life lived with disability (YLDs), which were added to the years of life lost due to premature mortality (YLLs), calculated from stroke mortality data, to obtain the DALYs. The results were extrapolated to the rest of Italy after examination of national stroke registries data. RESULTS: Standardized estimated incidence of FES in FVG in 1998 was lower (135 cases of FES per 100 000 inhabitants) than that reported in other published national and international studies. Estimated case fatality rate and distribution of post-FES disability did not differ from other similar studies. About 100 000 YLLs and 273 000 YLDs due to FES were estimated in 1998 for Italy. CONCLUSIONS: The estimated proportion of the YLDs on total DALYs (27%) is comparable with that obtained in the EURO-A group (the European area including Italy) of the GBD 2000 Study (31%), and the Australian BoD Study (35%).

Cost-effectiveness analysis of two rituximab retreatment regimens for longstanding rheumatoid arthritis.

OBJECTIVE: Rituximab (RTX) is licensed for second-line treatment of rheumatoid arthritis (RA) after first tumor necrosis factor (TNF) inhibitor failure. RTX is generally administered intravenously at 1 gm 2 weeks apart, and the retreatment is scheduled at the time of clinical relapse (regimen 1). A more intensive regimen is proposed with a fixed full cycle after 6 months (regimen 2) if remission is not reached. A cost-effectiveness analysis (CEA) compared these 2 regimens of RTX administration in patients with longstanding RA based on data provided by an observational study. METHODS: An observational retrospective study was conducted on 102 patients, enrolled in 3 hospitals and followed for ≥12 months. Forty-seven patients followed regimen 1, while 55 patients followed regimen 2. A CEA based on a Markov model was conducted. A lifelong and social perspective was adopted. CEA was conducted for the entire cohort and for the 2 subgroups separately (patients with positive rheumatoid factor and/or anti-cyclic citrullinated peptide and failures to TNF inhibitors). RESULTS: Results for the overall sample show at 10, 20, and 30 years that regimen 1 is less costly and associated with a higher quality of life compared to regimen 2. Probabilistic sensitivity analysis at 10 years estimated a probability of 95.1% for regimen 1 to be cost effective given a willingness to pay of €35,000/quality-adjusted life year, while for seropositive patients and for TNF failures it was estimated to be 92% and 92.7%, respectively. CONCLUSION: In longstanding RA, cost effectiveness of RTX retreatment at clinical relapse was found to be at least equivalent to the more intensive regimen proposed.

Impact of technology overlapping: a case study on colorectal cancer screening.

OBJECTIVES: Technology overlapping is a phenomenon based on the availability of different technologies to treat the same morbidity in the same patient group. The aim of this study was to explore the cost-effectiveness of technology overlapping in a case study on colorectal cancer (CRC), and describe an approach to investigate the phenomena and to propose adequate interventions. METHODS: A Semi-Markov model, based on a cohort of 10,000 people undergoing a CRC diagnostic test, was developed to simulate the overlapping phenomena and compare it with hypothetical scenarios where only one diagnostic tool is available. Deterministic sensitivity analyses were conducted on parameters with the greatest uncertainty. RESULTS: The results of the Semi-Markov model indicated that technology overlapping is not cost-effective. CONCLUSIONS: This study is a first attempt to address the significance of technology overlapping. The Semi-Markov model demonstrated that technology overlapping is the least cost-effective arm, so alternate health care policies must be investigated.