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.

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.

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.

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.

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.

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.

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.