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-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.

Direct healthcare costs of non-metastatic castration-resistant prostate cancer in Italy.

OBJECTIVES: The management of non-metastatic castration-resistant prostate cancer (nmCRPC) is rapidly evolving; however, little is known about the direct healthcare costs of nmCRPC. We aimed to estimate the cost-of-illness (COI) of nmCRPC from the Italian National Health Service perspective. METHODS: Structured, individual qualitative interviews were carried out with clinical experts to identify what healthcare resources are consumed in clinical practice. To collect quantitative estimates of healthcare resource consumption, a structured expert elicitation was performed with clinical experts using a modified version of a previously validated interactive Excel-based tool, EXPLICIT (EXPert eLICItation Tool). For each parameter, experts were asked to provide the lowest, highest, and most likely value. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to test the robustness of the results. RESULTS: Ten clinical experts were interviewed, and six of them participated in the expert elicitation exercise. According to the most likely estimate, the yearly cost per nmCRPC patient is €4,710 (range, €2,243 to €8,243). Diagnostic imaging (i.e., number/type of PET scans performed) had the highest impact on cost. The PSA showed a 50 percent chance for the yearly cost per nmCRPC patient to be within €5,048 using a triangular distribution for parameters, and similar results were found using a beta-PERT distribution. CONCLUSIONS: This study estimated the direct healthcare costs of nmCRPC in Italy based on a mixed-methods approach. Delaying metastases may be a reasonable goal also from an economic standpoint. These findings can inform decision-making about treatments at the juncture between non-metastatic and metastatic prostate cancer disease.

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.

How to Reduce Inequity of Access to Cardiac Rehabilitation After Surgical Aortic Valve Replacement. Recommendations for the Post-COVID-19 Era From a Real-World, Population-Based Study.

PURPOSE: Cardiac rehabilitation (CR) is a class I recommendation after valvular surgery. Few data exist on the level of access to CR after surgical aortic valve replacement (SAVR), and the factors affecting the probability of timely access to CR after SAVR have never been empirically investigated. This study aims at estimating the proportion of SAVR patients who initiated timely CR and understanding to what extent timely access to CR for SAVR patients is influenced by specific characteristics of patients and hospitals. METHODS: We conducted a real-world, retrospective, population-based study by identifying from the Italian National Hospital Discharge Records all the discharged alive SAVR patients who accessed timely CR from 2009-2016. Two different cutoffs for timely access were considered, i.e. one and 21 days after discharge. A unique dataset was constructed by merging several data sources. Multiple logistic regressions were performed to identify the factors influencing the probability to access to timely CR. FINDINGS: 107,545 patients underwent SAVR in Italy from 2009-2016 and were discharged alive. Overall, 71,593 SAVR patients (66.6%) accessed timely CR, with an increasing trend over time. Additional 6,149 patients (5.7%) started CR from 2-21 days after discharge, slightly decreasing over time. The probability of timely CR (one-day cutoff) was significantly higher in older (OR=1.025, p<0.001) female patients (OR = 1.003, p<0.05) and patients with cardiovascular and cerebrovascular comorbidities. Presence of rehabilitation wards and number of rehabilitation beds in the index hospital significantly increased the probability of timely access to CR (OR = 1.105, p<0.001 and OR = 1.006, p<0.001 respectively). Patients hospitalized in private teaching hospitals had the highest predicted probability of timely CR after SAVR. A substantial variation in access to CR was found across Italian regions. Similar results were obtained with the alternative 21-days cutoff. IMPLICATIONS: Approximately one-third of SAVR patients did not benefit from CR in Italy, mainly due to shortness of rehabilitation facilities, with relevant disparities across the country. The cessation of CR services during the COVID-19 pandemic provides the opportunity to re-think and innovate CR, shifting from center-based to home-based models. Digital health technologies can supplement traditional health services and grant safe, effective, and equitable access to care, especially for countries with insufficient rehabilitation bed capacity. As CR is associated with better outcomes, we recommend decision-makers to use our results to plan adequate healthcare services, also investing in digital health, to ensure patients' access to cost-effective care.

Disability weights for castration-resistant prostate cancer: an empirical investigation.

Introduction: Health state valuation and diagnostic-therapeutic pathways at the junction between non-metastatic and metastatic castration-resistant prostate cancer (CRPC) are not well documented. We aimed at: (i) estimating the disability weights (DWs) for health states across a continuum of disease from asymptomatic non-metastatic (nmCRPC) to symptomatic metastatic state (mCRPC); (ii) mapping the diagnostic-therapeutic pathway of nmCRPC in Italy. Methods: Structured qualitative interviews were performed with clinical experts to gather information on nmCRPC clinical pathway. An online survey was administered to clinical experts to estimate DWs for four CRPC health states defined from interviews and literature review (i.e., nmCRPC, asymptomatic mCRPC, symptomatic mCRPC, mCRPC in progression during or after chemotherapy). Clinicians' preferences for health states were elicited using the Person-Trade-Off (PTO) and Visual Analogue Scale (VAS) methods. DWs associated with each health state, from 0 (best imaginable health state) and 1 (worst imaginable health state), were estimated. Results: We found that the management of nmCRPC is heterogeneous across Italian regions and hospitals, especially with respect to diagnostic imaging techniques. DWs for PTO ranged from 0.415 (95% confidence interval [CI] 0.208-0.623) in nmCRPC to 0.740 (95% CI 0.560-0.920) in mCRPC, in progression during or after chemotherapy. DWs for VAS ranged between 0.246 (95% CI 0.131-0.361) in nmCRPC to 0.689 (95% CI 0.583-0.795) in mCRPC, in progression during or after chemotherapy. Conclusions: Estimated DWs suggest that delaying transition to a metastatic state might ease the disease burden at both patient and societal levels.

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.

Clinical outcomes and quality of life associated with the use of a biosynthetic mesh for complex ventral hernia repair: analysis of the "Italian Hernia Club" registry.

With the development of newer meshes and approaches to hernia repair, it is currently difficult to evaluate their performances while considering the patients' perspective. The aim of the study was to assess the clinical outcomes and quality of life consequences of abdominal hernia repairs performed in Italy using Phasix and Phasix ST meshes through the analysis of real-world data to support the choice of new generation biosynthetic meshes. An observational, prospective, multicentre study was conducted in 10 Italian clinical centres from May 2015 to February 2018 and in 15 Italian clinical centres from March 2018 to May 2019. The evaluation focused on patients with VHWG grade II-III who underwent primary ventral hernia repair or incisional hernia intervention with a follow-up of at least 18 months. Primary endpoints included complications' rates, and secondary outcomes focused on patient quality of life as measured by the EuroQol questionnaire. Seventy-five patients were analysed. The main complications were: 1.3% infected mesh removal, 4.0% superficial infection requiring procedural intervention, 0% deep/organ infection, 8.0% recurrence, 5.3% reintervention, and 6.7% drained seroma. The mean quality of life utility values ranged from 0.768 (baseline) to 0.967 (36 months). To date, Phasix meshes have proven to be suitable prostheses in preventing recurrence, with promising outcomes in terms of early and late complications and in improving patient quality of life.

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.

Cost-effectiveness and Net Monetary Benefit of Durvalumab Consolidation Therapy Versus No Consolidation Therapy After Chemoradiotherapy in Stage III Non-small Cell Lung Cancer in the Italian National Health Service.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness and net monetary benefit of durvalumab consolidation therapy compared with no consolidation therapy after chemoradiotherapy in patients with stage III non-small cell lung cancer with programmed cell death 1 ligand 1 expression ≥1% from the Italian National Health Service perspective. METHODS: We developed a 12-month decision tree combined with a lifetime cohort Markov model in which patients were assigned to receive durvalumab consolidation therapy or active follow-up (Italian standard of care) after chemoradiotherapy to compare cost-effectiveness and net monetary benefit of the two strategies during a 40-year period. Clinical outcomes data were obtained from the respective clinical trials and extrapolated using survival analysis; cost data were derived from Italian official sources and relevant real-world studies. The incremental cost-effectiveness ratio, incremental cost-utility ratio, and incremental net monetary benefit were computed and compared against a 16,372 € per quality-adjusted life-year (QALY) willingness-to-pay threshold. We performed deterministic sensitivity analysis and probabilistic sensitivity analysis to assess how uncertainty affected results; we also performed scenario analyses to compare results under different pricing settings. FINDINGS: In the base-case scenario, during a 40-year period, the total costs for patients treated with durvalumab consolidation therapy and active follow-up were €59,860 and €49,840 respectively; life-years gained were 3.47 and 3.31, respectively; and QALYs gained were 2.73 and 2.50, respectively, with an incremental cost-effectiveness ratio of €62,131 per life-year, an incremental cost-utility ratio of €42,322 per QALY, and an incremental net monetary benefit of €-6,144. We found that durvalumab was cost-effective (incremental net monetary benefit = 0) when a discount of 13% and 30% on its official price was applied, considering all other drugs priced according to official or maximum selling prices, respectively. Results were most sensitive to the progression-free survival rate for durvalumab and active follow-up, health utility in progression-free state, and price of subsequent treatments. IMPLICATIONS: Our analysis indicates that durvalumab consolidation is cost-effective when a discount is applied on its official price. These results suggest that durvalumab may deliver an incremental health benefit with a contained upfront cost during a 40-year period, from the Italian National Health Service perspective, providing added value in a potentially curative care setting.

Mapping health-related quality of life scores from FACT-G, FAACT, and FACIT-F onto preference-based EQ-5D-5L utilities in non-small cell lung cancer cachexia.

BACKGROUND: Health-related quality of life (HRQoL) measurements from disease-specific tools cannot be directly used in economic evaluations. This study aimed to develop and validate mapping algorithms that predicted EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) utilities from Functional Assessment of Anorexia-Cachexia Therapy (FAACT) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and their common component (Functional Assessment of Cancer Therapy-General-FACT-G) in patients with non-small cell lung cancer cachexia. METHODS: Data were collected on five occasions over a 12-week period in two multicenter placebo-controlled trials. EQ-5D-5L utilities were calculated using both English and Dutch value sets. The study sample was divided into development and validation datasets according to patients' geographical residence. Generalized estimating equations were applied to five different sets of independent variables including overall, Trial Outcome Index (TOI), and individual subscales results. The best performing models were selected based on mean absolute error (MAE) and root-mean square error (RMSE). RESULTS: EQ-5D-5L and FAACT/FACIT-F results were available for 96 patients. The developed algorithms showed a good predictive performance, with acceptable MAE/RMSE and small differences between mean observed and predicted EQ-5D-5L utilities. In FACT-G models, Physical Well-Being had the highest explanatory value, while Emotional Well-Being did not significantly affect the EQ-5D-5L score; Anorexia-Cachexia and Fatigue subscales were highly statistically significant in FAACT and FACIT-F models, respectively, as well as the TOI scores. The Eastern Cooperative Oncology Group status was included as covariate in all models. CONCLUSION: The developed algorithms enable the estimation of EQ-5D-5L utilities from three cancer-specific instruments when preference-based HRQoL data are missing.

Costs and effects of on-demand treatment of hereditary angioedema in Italy: a prospective cohort study of 167 patients.

OBJECTIVES: To explore treatment behaviours in a cohort of Italian patients with hereditary angioedema due to complement C1-inhibitor deficiency (C1-INH-HAE), and to estimate how effects and costs of treating attacks in routine practice differed across available on-demand treatments. DESIGN: Cost analyses and survival analyses using attack-level data collected prospectively for 1 year. SETTING: National reference centre for C1-INH-HAE. PARTICIPANTS: 167 patients with proved diagnosis of C1-INH-HAE, who reported data on angioedema attacks, including severity, localisation and duration, treatment received, and use of other healthcare services. INTERVENTIONS: Attacks were treated with either icatibant, plasma-derived C1-INH (pdC1-INH) or just supportive care. MAIN OUTCOME MEASURES: Treatment efficacy in reducing attack duration and the direct costs of acute attacks. RESULTS: Overall, 133 of 167 patients (79.6%) reported 1508 attacks during the study period, with mean incidence of 11 attacks per patient per year. Only 78.9% of attacks were treated in contrast to current guidelines. Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment (median times from onset 7, 10 and 47 hours, respectively), but remission rates with icatibant were 31% faster compared with pdC1-INH (HR 1.31, 95% CI 1.14 to 1.51). However, observed treatment behaviours suggest patterns of suboptimal dosing for pdC1-INH. The average cost per attack was €1183 (SD €789) resulting in €1.58 million healthcare costs during the observation period (€11 912 per patient per year). Icatibant was 54% more expensive than pdC1-INH, whereas age, sex and prophylactic treatment were not associated to higher or lower costs. CONCLUSIONS: Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment, however, icatibant was more effective but also more expensive. Treatment behaviours and suboptimal dosing of pdC1-INH may account for the differences, but further research is needed to define their role.