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

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

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

Health system quality and COVID-19 vaccination: a cross-sectional analysis in 14 countries.

The social and behavioural determinants of COVID-19 vaccination have been described previously. However, little is known about how vaccinated people use and rate their health system. We used surveys conducted in 14 countries to study the health system correlates of COVID-19 vaccination. Country-specific logistic regression models were adjusted for respondent age, education, income, chronic illness, history of COVID-19, urban residence, and minority ethnic, racial, or linguistic group. Estimates were summarised across countries using random effects meta-analysis. Vaccination coverage with at least two or three doses ranged from 29% in India to 85% in Peru. Greater health-care use, having a regular and high-quality provider, and receiving other preventive health services were positively associated with vaccination. Confidence in the health system and government also increased the odds of vaccination. By contrast, having unmet health-care needs or experiencing discrimination or a medical mistake decreased the odds of vaccination. Associations between health system predictors and vaccination tended to be stronger in high-income countries and in countries with the most COVID-19-related deaths. Access to quality health systems might affect vaccine decisions. Building strong primary care systems and ensuring a baseline level of quality that is affordable for all should be central to pandemic preparedness strategies.

Collecting Physicians' Preferences on Medical Devices: Are We Doing It Right? Evidence from Italian Orthopedists Using 2 Different Stated Preference Methods.

OBJECTIVES: Physician preference items (PPIs) are high-cost medical devices for which clinicians express firm preferences with respect to a particular manufacturer or product. This study aims to identify the most important factors in the choice of new PPIs (hip or knee prosthesis) and infer about the existence of possible response biases in using 2 alternative stated preference techniques. METHODS: Six key attributes with 3 levels each were identified based on a literature review and clinical experts' opinions. An online survey was administered to Italian hospital orthopedists using type 1 best-worst scaling (BWS) and binary discrete choice experiment (DCE). BWS data were analyzed through descriptive statistics and conditional logit model. A mixed logit regression model was applied to DCE data, and willingness-to-pay (WTP) was estimated. All analyses were conducted using Stata 16. RESULTS: A sample of 108 orthopedists were enrolled. In BWS, the most important attribute was "clinical evidence," followed by "quality of products," while the least relevant items were "relationship with the sales representative" and "cost." DCE results suggested instead that orthopedists prefer high-quality products with robust clinical evidence, positive health technology assessment recommendation and affordable cost, and for which they have a consolidated experience of use and a good relationship with the sales representative. CONCLUSIONS: The elicitation of preferences for PPIs using alternative methods can lead to different results. The BWS of type 1, which is similar to a ranking exercise, seems to be more affected by acquiescent responding and social desirability than the DCE, which introduces tradeoffs in the choice task and is likely to reveal more about true preferences. HIGHLIGHTS: Physician preference items (PPIs) are medical devices particularly exposed to physicians' choice with regard to type of product and supplier.Some established techniques of collecting preferences can be affected by response biases such as acquiescent responding and social desirability.Discrete choice experiments, introducing more complex tradeoffs in the choice task, are likely to mitigate such biases and reveal true physicians' preferences for PPIs.

Cost-effectiveness analysis of pressure-controlled intermittent coronary sinus occlusion in elective percutaneous coronary intervention.

OBJECTIVES: Percutaneous coronary intervention (PCI) represents the standard treatment for ST-elevated myocardial infarction, nevertheless, mortality and heart failures are frequent. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) might reduce infarct size showing better patients' outcomes. We evaluated the cost-effectiveness of PCI+PiCSO compared to PCI from the National Healthcare Service (NHS) perspective in Italy. METHODS: A Markov model was developed to estimate life years (LYs), quality-adjusted life years (QALYs) and costs. A micro-costing analysis has been performed to inform the cost of PCI+PiCSO procedure. Sensitivity analyses were performed to test the robustness of the model results. RESULTS: Considering a willingness-to-pay threshold of 50,000€/QALY for the ICUR and a cost for PCI+PiCSO procedure of 14,654€, the innovative strategy may be cost-effective compared to PCI alone from the Italian NHS perspective, showing an ICUR of 17,530€/QALY (ICER 14,631€/LY) over a lifetime horizon; the probabilistic sensitivity analysis showed that PCI+PiCSO is cost-effective in 78.8% of simulations.Considering the above mentioned willingness-to-pay threshold, PCI+PiCSO strategy would be cost-effective over a lifetime horizon considering a cost for PCI+PiCSO procedure lower than 28,160€. CONCLUSION: PCI+PiCSO procedure may be considered a cost-effective technology that allows reducing cardiac events, while improving patients' life expectancy and quality of life.

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

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

Early access programs for medicines: comparative analysis among France, Italy, Spain, and UK and focus on the Italian case.

Early access programs (EAPs) generally refer to patient access to medicines/indications before marketing authorization, possibly extended to price and reimbursement approval. These programs include compassionate use, which is usually covered by pharmaceutical companies, and EAPs reimbursed by third-party payers. This paper aims at comparing EAPs in four European countries (France, Italy, Spain, UK) and providing empirical evidence on EAPs in Italy. The comparative analysis was conducted through a literature review (including scientific and grey literature), complemented by 30-min semi-structured interviews with local experts. The Italian empirical analysis employed data available on the National Medicines Agency website. Although EAPs are very different across countries, they exhibit some common features: (i) eligibility criteria refer to the absence of valid therapeutic alternatives and a presumed favourable risk-benefit profile; (ii) payers do not allocate a pre-determined budget to these programs; (iii) total spending on EAPs is unknown. The French EAPs seem to be the most structured, financed through social insurance, covering pre-marketing, post-marketing and pre-reimbursement phases and providing for data collection. Italy's approach to EAPs has been varied, with several programs covered by different payers, including the cohort-based 648 List (for both early access and off-label use), the nominal-based 5% Fund, and Compassionate Use. Most applications to EAPs are from the Antineoplastic and immunomodulating drug class (ATC L). Some 62% of indications in the 648 List are either not under clinical development or have never been approved (pure off-label use). For those subsequently approved, most approved indications coincide with those covered through EAPs. Only the 5% Fund provides data on economic impact (€ 81.2 million in 2021; average cost per patient € 61.5K). Diverse EAPs are a possible source of inequalities in access to medicines across Europe. A harmonization of these programs, though difficult to achieve, could be modelled on the French EAPs and provide key advantages, not least of which a common effort to collect real-world data in parallel with clinical trials and clear separation between EAPs and off-label use programs.

Cost-minimization analysis to support the HTA of Radiofrequency Echographic Multi Spectrometry (REMS) in the diagnosis of osteoporosis.

Introduction: A timely diagnosis of osteoporosis is key to reducing its growing clinical and economic burden. Radiofrequency Echographic Multi Spectrometry (REMS), a new diagnostic technology using an ultrasound approach, has been recognized by scientific associations as a facilitator of patients' care pathway. We aimed at evaluating the costs of REMS vs. the conventional ionizing technology (dual-energy X-ray absorptiometry, DXA) for the diagnosis of osteoporosis from the perspective of the Italian National Health Service (NHS) using a cost-minimization analysis (CMA). Methods: We carried out structured qualitative interviews and a structured expert elicitation exercise to estimate healthcare resource consumption with a purposeful sample of clinical experts. For the elicitation exercise, an Excel tool was developed and, for each parameter, experts were asked to provide the lowest, highest and most likely value. Estimates provided by experts were averaged with equal weights. Unit costs were retrieved using different public sources. Results: Considering the base-case scenario (most likely value), the cost of professionals amounts to €31.9 for REMS and €48.8 for DXA, the cost of instrumental examinations and laboratory tests to €45.1 for REMS and €68.2 for DXA. Overall, in terms of current costs, REMS is associated with a mean saving for the NHS of €40.0 (range: €27.6-71.5) for each patient. Conclusions: REMS is associated with lower direct healthcare costs with respect to DXA. These results may inform policy-makers on the value of the REMS technology in the earlier diagnosis for osteoporosis, and support their decision regarding the reimbursement and diffusion of the technology in the Italian NHS.

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

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

Use of Resource Modeling to Quantify the Organizational Impact of Subcutaneous Formulations for the Treatment of Oncologic Patients: The Case of Daratumumab in Multiple Myeloma.

PURPOSE: Resource modeling aims to explicitly quantify the effects of adopting new health care technologies in settings with capacity-related constraints. The aim of this analysis was to use resource modeling to explore the effects of the uptake of first-line treatment with daratumumab on wait lists and wait times in patients with untreated multiple myeloma. Two formulations were compared: the standard IV formulation (DARA-IV) and a recently approved SC formulation (DARA-SC). METHODS: First, semi-structured interviews at six oncologic centers were used to retrieve data on the management of patients given a DARA-IV regimen. Second, a discrete event simulation (DES) model was built to estimate the effects on resource consumption, wait lists, and wait times in scenarios with different incident numbers of patients treated with either DARA-IV or DARA-SC. FINDINGS: In all of the simulated scenarios with more incident patients initiated on first-line treatment with DARA-IV, the actual capacity of infusion chairs was not enough to meet the demand, leading to increases in wait times and wait lists. In the highest-demand scenario, 17 more infusion chairs per center would be required to avoid such increases. Treatment with DARA-SC would allow centers to meet the demand with their actual capacity. IMPLICATIONS: DES modeling can effectively be used to formally explore the effects of different formulations on the use of limited resources, wait lists, and wait times at the facility level. Based on the findings from this analysis, DARA-SC may free up resources and prevent short- and long-term costs to infusion centers.

Digital Twins in Healthcare: Is It the Beginning of a New Era of Evidence-Based Medicine? A Critical Review.

Digital Twins (DTs) are used in many different industries (e.g., manufacturing, construction, automotive, and aerospace), and there is an initial trend of applications in healthcare, mainly focusing on precision medicine. If their potential is fully unfolded, DTs will facilitate the as-yet-unrealized potential of connected care and alter the way lifestyle, health, wellness, and chronic disease will be managed in the future. To date, however, due to technical, regulatory and ethical roadblocks, there is no consensus as to what extent DTs in healthcare can introduce revolutionary applications in the next decade. In this review, we present the current applications of DTs covering multiple areas of healthcare (precision medicine, clinical trial design, and hospital operations) to identify the opportunities and the barriers that foster or hinder their larger and faster diffusion. Finally, we discuss the current findings, opportunities and barriers, and provide recommendations to facilitate the continuous development of DTs application in healthcare.

The invisible costs of obstructive sleep apnea (OSA): Systematic review and cost-of-illness analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for several diseases and is correlated with other non-medical consequences that increase the disease's clinical and economic burden. However, OSA's impact is highly underestimated, also due to substantial diagnosis gaps. OBJECTIVE: This study aims at assessing the economic burden of OSA in the adult population in Italy by performing a cost-of-illness analysis with a societal perspective. In particular, we aimed at estimating the magnitude of the burden caused by conditions for which OSA is a proven risk factor. METHODS: A systematic literature review on systematic reviews and meta-analyses, integrated by expert opinion, was performed to identify all clinical and non-clinical conditions significantly influenced by OSA. Using the Population Attributable Fraction methodology, a portion of their prevalence and costs was attributed to OSA. The total economic burden of OSA for the society was estimated by summing the costs of each condition influenced by the disease, the costs due to OSA's diagnosis and treatment and the economic value of quality of life lost due to OSA's undertreatment. RESULTS: Twenty-six clinical (e.g., diabetes) and non-clinical (e.g., car accidents) conditions were found to be significantly influenced by OSA, contributing to an economic burden ranging from €10.7 to €32.0 billion/year in Italy. The cost of impaired quality of life due to OSA undertreatment is between €2.8 and €9.0 billion/year. These costs are substantially higher than those currently borne to diagnose and treat OSA (€234 million/year). CONCLUSIONS: This study demonstrates that the economic burden due to OSA is substantial, also due to low diagnosis and treatment rates. Providing reliable estimates of the economic impact of OSA at a societal level may increase awareness of the disease burden and help to guide evidence-based policies and prioritisation for healthcare, ultimately ensuring appropriate diagnostic and therapeutic pathways for patients.

Cost per responder of Adalimumab biosimilars MSB11022 and ABP 501 versus the originator and methotrexate in chronic plaque psoriasis.

BACKGROUND: Pharmacoeconomic studies comparing the cost of adalimumab biosimilars versus the originator and conventional drugs in psoriasis are lacking. RESEARCH DESIGN AND METHODS: To assess the cost per responder of adalimumab biosimilars versus the originator and methotrexate for psoriasis treatment. A cost per responder analysis comparing adalimumab biosimilars MSB11022 (Idacio®) and ABP 501 (Amgevita®), and methotrexate to the originator (Humira®) was performed. The incremental cost per responder was calculated by multiplying the cost of treatment based on the perspective of the National Healthcare System and number needed to treat for each therapy. RESULTS: Considering the PASI75 response rate at 16 weeks, the cost per responder for MSB11022 and ABP 501 compared to the originator was € 500 versus 1,831 and € 968 versus 1,949, respectively. For the same endpoint, the cost per responder for subcutaneous or oral methotrexate was € 543 or 34 compared to 2,117 for adalimumab originator. At an indirect comparison among methotrexate, MSB11022 and ABP 501, the costs per PASI75 responder at week 16 were 2%, 26%, 27% and 50% of that of the originator, respectively. CONCLUSIONS: The use of biosimilars was confirmed as a valuable pharmacoeconomic strategy to lower healthcare cost in patients with psoriasis.

The Value of Hearing Aids for the Italian NHS: A Cost-utility Analysis.

Objective: Hearing loss (HL) prevalence in Italy is expected to increase due to population aging. Hearing aids (HAs) are the main tool for HL rehabilitation; however, cost-utility analyses of HAs are limited. Our objective was to estimate the cost-utility of HAs use. Study Design: Cost-utility analysis. Setting: Italian National Healthcare Service, societal perspective. Patients Interventions and Main Outcome Measures: A multistate Markov model was developed to model a cohort of 55-year-old individuals starting from normal hearing and moving across HL states to compare cost-utility and net monetary benefit of HA use accompanied by post-purchase service, HA use alone, and no treatment. Parameters were estimated using secondary data. Incremental cost-utility ratio (ICUR) and incremental net monetary benefit (INMB) were computed against a €16,625/quality-adjusted life year (QALY) willingness-to-pay (WTP) threshold. Deterministic and probabilistic sensitivity analysis (DSA, PSA) was implemented to assess how uncertainty affected results. Scenario analysis was performed on different assumptions on costs, dropout and compliance rates. Results: The model suggests HAs use is a cost-effective strategy compared to no treatment (in the base case: incremental costs €429-€476, incremental QALY gain 0.18 and 0.19, ICUR €2'404/QALY-€2'450/QALY, INMB €2'476-€2'682 for male and female cohort, respectively). By assuming no dropout, INMBs increase up to €10,643-€10,728. DSA highlights that utility weights contribute the most to model uncertainty, PSA shows that the treatment has 97.8%-97.3% probability of being cost-effective at the WTP threshold considered. Conclusions: We proposed an original model to assess the cost-utility of HAs use; the application to the Italian setting suggests the treatment is cost-effective, reinforcing the importance of early uptake.

[Early access programs and managed entry agreements for medicines in Italy: results of a Focus Group (Early Access Programs and Managed Entry Agreement).] / Programmi di early access dei farmaci e managed entry agreement in Italia: i risultati di un Focus Group (programmi di early access e managed entry agreement).

BACKGROUND: Early access of medicines occurs with an uncertainty in the evidence even higher than the one experienced when price and reimbursement status is negotiated. Our aim is discussing the role of managed entry agreements (MEA) within early access programs (EAP) in Italy. METHODS: The discussion relied on a Focus Group, participated by twelve experts, including clinicians and representatives of regulatory authorities, regional and local pharmaceutical departments, pharmaceutical companies, and an association advocating for active citizenship. RESULTS: The Focus Group emphasised that the topic under discussion should be embedded into a more general reform of EAP in Italy. The 648 List mostly includes mature products and indications that are rarely launched into the market afterwards. The 5% Fund is affected by an important administrative burden uncertainty of the timing of reimbursement. CONCLUSIONS: Starting from the discussion on MEA and EAP, the Focus Group recommended a new legislation better regulating EAP, that early access concerns specific classes of medicines selected on the grounds of the need to guarantee a rapid access and to collect real world data, that early access can be accompanied by outcome-based and population-based MEA, and that MEA are embedded into the subsequent price and reimbursement negotiation.

Establishing a national HTA program for medical devices in Italy: Overhauling a fragmented system to ensure value and equal access to new medical technologies.

Differing contexts have greatly influenced HTA development in various countries, with considerable effort recently made by international HTA networks (e.g., EUnetHTA) and the European Union (EU) to make HTA a more coherent, equal, and efficient process. Medical devices (MDs) present particular challenges for HTA because of frequent, rapid innovation, outcomes influenced by end-user competence, dynamic pricing and often low-quality scientific evidence. Our objective is to describe the development, structure and governance of a National HTA Program for MDs (PNHTADM) in Italy, a highly participatory, stakeholder-engaged, evidence-based process to reform a fragmented system of appraisal and approval. Based largely on EUnetHTA methods, the resulting process delineates a standardized system for proposing MDs by any stakeholders, accrediting HTA producers, setting criteria for prioritization and appraisals, and innovatively linking recommendations with coverage, reimbursement and procurement of MDs. Expected benefits include reduced disparities in pricing and reimbursement policies and improved access to new technologies across 21 regional healthcare systems in Italy's decentralized, universal system, complete with provisions to require additional evidence collection and centrally monitor diffusion. Though devised for Italy, the design, resources and underlying analysis provide a framework for other nations seeking to consolidate HTA initiatives, particularly in light of new EU regulation.

Reflections on the Importance of Cost of Illness Analysis in Rare Diseases: A Proposal.

In the field of rare diseases (RDs), the evidence standard is often lower than that required by health technology assessment (HTA) and payer authorities. In this commentary, we propose that appropriate economic evaluation for rare disease treatments should be initially informed by cost-of-illness (COI) studies conducted using a societal perspective. Such an approach contributes to improving countries' understanding of RDs in their entirety as societal and not merely clinical, or product-specific issues. In order to exemplify how the disease burden's distribution has changed over the last fifteen years, key COI studies for Hemophilia, Fragile X Syndrome, Cystic Fibrosis, and Juvenile Idiopathic Arthritis are examined. Evidence shows that, besides methodological variability and cross-country differences, the disease burden's share represented by direct costs generally grows over time as novel treatments become available. Hence, to support effective decision-making processes, it seems necessary to assess the re-allocation of the burden produced by new medicinal products, and this approach requires identifying cost drivers through COI studies with robust design and standardized methodology.

Social Economic Costs, Health-Related Quality of Life and Disability in Patients with Cri Du Chat Syndrome.

Background: Cri du Chat syndrome (CdC) is a rare disease caused by the deletion on the short arm of the chromosome 5, with an incidence of 1:15,000 to 1:50,000 live-born infants. No study at international level has assessed the costs, Quality of Life (QoL) and Disability through standardized quantitative tools. The aim is to estimate economic costs related to CdC from a societal perspective, to assess the QoL and Disability in patients with CdC along with their caregivers in Italy. Methods: A cross-sectional study of patients with Cri du Chat in Italy was carried out. A cost of illness approach from a societal perspective was used to estimate cost, and a micro-costing method was adopted. The QoL was measured with EuroQol 5-domain (EQ-5D) questionnaire and Disability by using World Health Organization Disability Assessment Schedule 36 item (WHODAS 2.0). Results: A total of 76 questionnaires were collected from caregivers taking care of 40 adult patients and 36 minor patients. All patients need a carer and the principal caregiver is commonly informal carer or a family member (93%). The EQ-5D VAS score for patients is 65.5 (SD = 22.4) out of 100; while the most important compromised areas of QoL are usual activities and self-care. The overall WHODAS 2.0 score is 65% (0 = no disability; 100 = full disability). The average annual cost of a patient with Cri du Chat in our population is €87,856.24; the main cost item of patients with Cri du Chat syndrome is informal care (i.e., €76,981.69 yearly) since it constitutes the 87% of total costs. Results highlight the burden of CdC in terms of its impact on QoL and Disability for patients and caregivers in Italy, with a score much lower than that of general population. The disease is associated with considerable costs of informal care. Conclusions: Cri du Chat syndrome was found to be linked with a significant socioeconomic impact which is dominated by direct non-healthcare informal costs.

Cost-Effectiveness and Net Monetary Benefit of Olaparib Maintenance Therapy Versus No Maintenance Therapy After First-line Platinum-based Chemotherapy in Newly Diagnosed Advanced BRCA1/2-mutated Ovarian Cancer in the Italian National Health Service.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness and net monetary benefit of olaparib maintenance therapy compared with no maintenance therapy after first-line platinum-based chemotherapy in newly diagnosed advanced BRCA1/2-mutated ovarian cancer from the Italian National Health Service (NHS) perspective. METHODS: We developed a lifetime Markov model in which a cohort of patients with newly diagnosed advanced BRCA1/2-mutated ovarian cancer was assigned to receive either olaparib maintenance therapy or active surveillance (Italian standard of care) after first-line platinum-based chemotherapy to compare cost-effectiveness and net monetary benefit of the 2 strategies. Data on clinical outcomes were obtained from related clinical trial literature and extrapolated using parametric survival analyses. Data on costs were derived from Italian official sources and relevant real-world studies. The incremental cost-effectiveness ratio (ICER), incremental cost-utility ratio (ICUR), and incremental net monetary benefit (INMB) were computed and compared against an incremental cost per quality-adjusted life-year (QALY) gained of €16,372 willingness-to-pay (WTP) threshold. We used deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) to assess how uncertainty affects results; we also performed scenario analyses to compare results under different pricing settings. FINDINGS: In the base-case scenario, during a 50-year time horizon, the total costs for patients treated with olaparib therapy and active surveillance were €124,359 and €97,043, respectively, and QALYs gained were 7.29 and 4.88, respectively, with an ICER of €9,515 per life-year gained, an ICUR of €11,345 per QALY gained, and an INMB of €12,104. In scenario analyses, considering maximum selling prices for all other drugs, ICUR decreased to €11,311 per QALY and €7,498 per QALY when a 10% and 20% discount, respectively, was applied to the olaparib official price, and the INMB increased to €12,186 and €21,366, respectively. DSA found that the model results were most sensitive to the proportion of patients with relapsing disease in response to platinum-based chemotherapy, time receiving olaparib first-line maintenance treatment, and subsequent treatments price. According to PSAresults, olaparib was associated with a probability of being cost-effective at a €16,372 per QALY WTP threshold ranging from 70% to 100% in the scenarios examined. IMPLICATIONS: Our analysis indicates that olaparib maintenance therapy may deliver a significant health benefit with a contained upfront cost during a 50-year time horizon, from the Italian NHS perspective, providing value in a setting with curative intent.