Baseline Assessment of Serum Cytokines Predicts Clinical and Endoscopic Response to Ustekinumab in Patients With Crohn's Disease: A Prospective Pilot Study.

BACKGROUND: No biomarkers are currently available to predict therapeutic response to ustekinumab (UST) in Crohn's disease (CD). The aim of this prospective study was to identify 1 or more cytokines able to predict mucosal healing in patients with CD treated with UST. METHODS: We prospectively enrolled consecutive CD patients treated with UST. At weeks 0 (baseline), 24, and 48, a panel of serum cytokines was measured by a fluorescence assay. At the same time points, fecal calprotectin (FC) was assessed. A colonoscopy was performed at baseline and at week 48, where therapeutic outcome was evaluated in terms of mucosal healing. RESULTS: Out of 44 patients enrolled, 22 (50%) achieved mucosal healing at the end of follow-up. Response was associated with higher interleukin (IL)-23 levels (P < .01). Fecal calprotectin levels decreased over time in responders but did not change in nonresponders (test for the interaction between time and mucosal healing, P < .001). CONCLUSIONS: This pilot study showed that IL-23 and FC could be reliable biomarkers in predicting therapeutic outcome to UST therapy in CD. In particular, the correlation between baseline serum levels of IL-23 and mucosal healing at 48 weeks is particularly strong, paving the way for its use to drive therapeutic decisions.

This prospective pilot study showed that the assessment of IL-23 levels at baseline could predict clinical and endoscopic outcomes to ustekinumab therapy in Crohn's disease. Testing this biomarker before starting a biological therapy could be useful for a personalized choice.

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.

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.

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.

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.

An observational analysis of costs and effectiveness of an intraoperative compared with a preoperative image-guided system in spine surgery fixation: analysis of 10 years of experience.

BACKGROUND: Image-guided navigation systems are well established technologies; their use in clinical practice is constantly growing. To date many publications have demonstrated their accuracy and safety. However, the acquisition and maintenance costs are high. In an era in which health expenditures are rising exponentially, analyses of the economic impact of new technologies are mandatory to assess their sustainability. METHODS: This is a retrospective analysis to assess the overall costs of a series of patients admitted to our Department of Neurosurgery for spinal instrumentation. We compared two different types of spinal navigation systems: based on preoperative CT scan (January 2003-April 2009) and on intraoperative CT-like scan (April 2009-March 2013). We used a micro-costing approach by a hospital perspective considering all the phases of the treatment process, from preadmission testing to discharge. RESULTS: The study includes 875 patients. Baseline data, hospitalization and complications were similar for both. Mean cost was € 7305.9 for intraoperative CT scan procedure and € 7666.2 for preoperative image-guided system. The effectiveness, in terms of screw accuracy was similar. Higher costs were related to implanted materials, human resources, and disposable. CONCLUSIONS: There was a statistically significant difference between the two groups in terms of costs. A break-even point for the acquisition of an intraoperative image system is calculated in almost 130 procedures. Moreover, nowadays this system is used for more than only screw insertion reducing the financial impact of this technology on a hospital.

Neuroscience20 (BRAIN20, SPINE20, and MENTAL20) Health Initiative: A Global Consortium Addressing the Human and Economic Burden of Brain, Spine, and Mental Disorders Through Neurotech Innovations and Policies.

Neurological disorders significantly impact the world's economy due to their often chronic and life-threatening nature afflicting individuals which, in turn, creates a global disease burden. The Group of Twenty (G20) member nations, which represent the largest economies globally, should come together to formulate a plan on how to overcome this burden. The Neuroscience-20 (N20) initiative of the Society for Brain Mapping and Therapeutics (SBMT) is at the vanguard of this global collaboration to comprehensively raise awareness about brain, spine, and mental disorders worldwide. This paper aims to provide a comprehensive review of the various brain initiatives worldwide and highlight the need for cooperation and recommend ways to bring down costs associated with the discovery and treatment of neurological disorders. Our systematic search revealed that the cost of neurological and psychiatric disorders to the world economy by 2030 is roughly $16T. The cost to the economy of the United States is $1.5T annually and growing given the impact of COVID-19. We also discovered there is a shortfall of effective collaboration between nations and a lack of resources in developing countries. Current statistical analyses on the cost of neurological disorders to the world economy strongly suggest that there is a great need for investment in neurotechnology and innovation or fast-tracking therapeutics and diagnostics to curb these costs. During the current COVID-19 pandemic, SBMT, through this paper, intends to showcase the importance of worldwide collaborations to reduce the population's economic and health burden, specifically regarding neurological/brain, spine, and mental disorders.

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.

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.

Assessment of serum cytokines predicts clinical and endoscopic outcomes to vedolizumab in ulcerative colitis patients.

AIMS: Vedolizumab (VDZ) prevents migration of activated leucocytes into inflamed mucosa. This study aimed to assess the patterns of serum cytokines in ulcerative colitis (UC) patients at baseline and during VDZ treatment, and to investigate their association with mucosal healing and clinical remission. METHODS: We enrolled consecutive UC patients eligible for treatment with VDZ. A panel of serum cytokines were measured by fluorescence assay at weeks 0, 6 and 22. Colonoscopy was performed at baseline and week 54, to evaluate mucosal healing. The time trends of serum cytokines were analysed by log-linear mixed effect models, and their prognostic accuracy was evaluated by logistic regression. RESULTS: Out of 27 patients included in the analysis, at week 54 mucosal healing was achieved in 12 (44%) and clinical remission in 17 (63%). Mucosal healing was associated with higher interleukin (IL)-8 values at baseline and with significant decrease in IL-6 and IL-8 levels over the first 6 weeks. A significant reduction of IL-6 and IL-8 levels over the first 6 weeks of treatment was associated also with clinical remission. Logistic models including, among the predictors, IL-6 and IL-8 at baseline and their changes over the first 6 weeks of treatment had 83% sensitivity and 87% specificity to predict mucosal healing, and 82% sensitivity and 90% specificity to predict clinical remission. CONCLUSION: In UC patients, the serum patterns of IL-6 and IL-8 at baseline and over the first 6 weeks of treatment with VDZ could be useful to predict therapeutic outcome.

Implementation of Value-based Pricing for Medicines.

Value-based pricing (VBP) is well established in markets for common goods and services, but wide consensus on VBP for pharmaceuticals is lacking. In principle, VBP implies that prices are mainly driven by a drug's value (value for money) and that the impact on budget (sustainability) is a second-order driver of price regulation. Although the literature provides descriptive analyses on regulations governing medicine price negotiation, there are few insights on whether and how price negotiation regulations have been implemented. The goal of this article was to cover this information gap for 5 European countries and the United States. VBP has been applied according to two models: (1) direct models in which cost-effectiveness is a driver; and (2) indirect, multi-attribute models characterized by greater discretion on the integration between the different value domains and the evaluation of consistency between costs and value. In these models, cost-effectiveness is not a driver. In addition, it is hard to evaluate within these models the actual implementation of VBP. Identifying whether and how VBP is applied requires a clear predefined link between added value and the premium price, as well as transparency in the way added value is converted into a premium price. In general, for these countries, it remains difficult to determine whether pricing is mostly driven by value (value-for-money) or impact on budget (sustainability). In instances in which thresholds on the incremental cost-effectiveness ratio are used, it becomes easier to understand whether VBP has been implemented. If VBP relies on a multi-criteria approach, greater transparency on which criteria have been used to assess a new drug and how they have been converted into a reasonable price may help in understanding whether a value-based approach has been used.

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC).

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.

Health care costs of influenza-related episodes in high income countries: A systematic review.

INTRODUCTION: This study systematically reviews costing studies of seasonal influenza-like illness (ILI) in high-income countries. Existing reviews on the economic impact of ILI do not report information on drug consumption and its costs, nor do they provide data on the overall cost per episode. METHODS: The PRISMA-P checklist was used to design the research protocol. Studies included were cost of illness analysis (COI) and modeling studies that estimated the cost of ILI episodes. Records were searched from January 2000 to December 2016 in electronic bibliographic databases including Medline, Embase, Science Direct, the Cochrane Library, the Centre for Reviews and Disseminations of the University of York, and Google scholar. References from the included studies were hand-searched for completion. Abstract screening, full-text analysis and data extraction were performed by two reviewers independently and discrepancies were resolved by discussion with a third reviewer. A standardized, pre-piloted form was used for data extraction. All costs were converted to 2015 US$ Purchasing Power Parities. RESULTS: The literature search identified 5,104 records. After abstract and title screening, 76 studies were analyzed full-text and 27 studies were finally included in the review. Full estimates of the cost per episode range from US$19 in Korea to US$323 in Germany. Particularly, the cost per episode of laboratory confirmed influenza cases was estimated between US$64 and US$73. Inpatient and outpatient services account for the majority of the costs. Differences in the estimates may reflect country-specific characteristics, as well as other study-specific features including study design, identification strategy of ILI cases, study populations and types of costs included in the analysis. Children usually register higher costs, whereas evidence for the elderly is less conclusive. Patients risk-profile, co-morbidities and complications are the other important cost-drivers. None of the papers considered appropriateness in resource use (e.g. abuse of antibiotics). Despite cost of illness studies have ultimately a descriptive role, evidence on (in)appropriateness is useful for policy-makers.

Is surgical resection useful in elderly newly diagnosed glioblastoma patients? Outcome evaluation and prognostic factors assessment.

ASTRACT: BACKGROUND: The incidence of glioblastoma among elderly patients is constantly increasing. The value of radiation therapy and concurrent/adjuvant chemotherapy has been widely assessed. So far, the role of surgery has not been thoroughly investigated. The study aimed to evaluate safety and impact of several entities of surgical resection on outcome of elderly patients with newly diagnosed glioblastoma treated by a multimodal approach. METHODS: Patients ≥ 65 years, underwent surgery were included. The extent of surgical resection (EOR) was defined as complete resection (CR = 100%), gross total resection (GTR = 90-99%), sub-total resection (STR = 78-90%), partial resection (PR = 30-78%), and biopsy. After surgery, all patients received adjuvant radiotherapy (60/2 Gy fraction) with concomitant/adjuvant temozolomide chemotherapy. RESULTS: From March 2004 to December 2015, 178 elderly with a median age of 71 years (range 65-83 years) were treated. CR was obtained in 8 (4.5%), GTR in 63 (35.4%), STR in 46 (25.8%), PR in 16 (9.0%), and biopsy in 45 (25.3%). RT was started in all patients, concurrent/adjuvant CHT in 149 (83.7%) and 132 (74.2%). The median follow-up time was 12.2 months (range 0.4-50.4 months). The median, 1- and 2-year progression-free survival was 8.9 months (95%CI 7.8-100 months), 32.0 ± 3.5%, and 12.9 ± 2.6%. The median, 1- and 2-year overall survival were 12.2 (95%CI 11.3-13.1 months), 51.1 ± 3.7%, and 16.3 ± 2.9%. Tumor location, extent of resection, and neurological status after surgery statistically affected survival (p ≪ 0.01). CONCLUSION: Maximal surgical resection is safe and feasible in elderly patients with influence on survival. A preoperative evaluation has to be carried out.

Therapeutic Drug Monitoring is More Cost-Effective than a Clinically Based Approach in the Management of Loss of Response to Infliximab in Inflammatory Bowel Disease: An Observational Multicentre Study.

BACKGROUND AND AIMS: Empirical dose intensification and therapeutic drug monitoring [TDM] of infliximab [IFX] trough levels [ITLs] and antibody to infliximab [ATI] assays are recognized approaches for managing loss of response [LoR] in patients with inflammatory bowel disease [IBD]. The aim of the study was to compare these two interventions in a clinical setting, in terms of effectiveness and cost savings. METHODS: Consecutive IBD patients experiencing LoR were clinically managed according to a TDM algorithm. A historical group of empirically treated patients, for whom sera for ITLs and ATI assays had been collected, served as the control group. Clinical outcomes 12 weeks after the therapeutic interventions were compared between the two groups. A cost-minimization analysis was performed to compare the economic impact of these two approaches. RESULTS: Ninety-six patients were enrolled prospectively and compared with 52 controls. The two cohorts were similar in characteristics and in the distribution of TDM results. In the prospective cohort, however, we observed less IFX dose escalations compared with in the controls [45% versus 71%, p = 0.003]. Also, more patients were switched to a different anti-TNFα in the prospective cohort than in the control cohort [25% versus 4%, p = 0.001]. The percentages of patients achieving a clinical response at 12 weeks were 52% and 54% for the prospective and control groups, respectively. By cost analysis, we estimated a savings of 15% if the TDM algorithm was applied. CONCLUSIONS: In our population, applying a TDM algorithm for LoR to IFX resulted in less dose escalations, without loss of efficacy, compared with empirical adjustment. In addition, the TDM approach was cost-effective.

Improving Adherence to Treatment and Reducing Economic Costs of Hypertension: The Role of Olmesartan-Based Treatment.

Poor adherence to antihypertensive treatment is the single most important factor of unsatisfactory blood pressure (BP) control. This review focuses on therapy-related factors affecting adherence and suggests how to improve it with a wise choice of treatment schedule. Complex drug treatment schemes, poor tolerability and drug substitutions are frequent causes of poor adherence which, in turn, causes insufficient BP control, greater incidence of cardiovascular events and, finally, higher global health costs. The effects of prescribing generic drugs and of drug substitutions on adherence is also discussed. In terms of adherence, generic drugs do not seem to be better than branded drugs, unless patients have to bear very high "out of pocket" expenses to buy original drugs, suggesting no advantages in switching drug with the mere goal of reducing the cost of therapy. An important role in improving adherence (and thus cardiovascular events and health expenditure) is also played by the availability of fixed-dose combinations; among antihypertensive drugs, angiotensin receptor blockers (ARBs) are those associated with higher levels of adherence and persistence. Among ARBs, olmesartan stands out for a wide choice of effective fixed-dose combinations.

Economic study: a cost-effectiveness analysis of an intraoperative compared with a preoperative image-guided system in lumbar pedicle screw fixation in patients with degenerative spondylolisthesis.

BACKGROUND CONTEXT: In spinal surgery, newly developed technology seems to play a key role, especially with the use of computer-assisted image-guided navigation, giving excellent results. However, these tools are expensive and may not be affordable for many facilities. PURPOSE: To compare the cost-effectiveness of preoperative versus intraoperative CT (computed tomography) guidance in spinal surgery. STUDY DESIGN: A retrospective economic study. METHODS: A cost-effectiveness study was performed analyzing the overall costs of a population of patients operated on for lumbar degenerative spondylolisthesis using an image-guided system (IGS) based on a CT scan. The population was divided into two groups according to the type of CT data set acquisition adopted: Group I (IGS based on a preoperative spiral CT scan), Group II (IGS based on an intraoperative CT scan-O-Arm system). The costs associated with each procedure were assessed through a process analysis, where clinical procedures were broken down into single phases and the related costs from each phase were evaluated. No benefits in any form have been or will be received from commercial parties directly or indirectly related to the subject of this article. RESULTS: Four hundred ninety-nine patients met the criteria for this study. In total, 2,542 screws were inserted with IGS. Baseline data were similar for the two groups, as were hospitalization and complications. The surgical time was 119±43 minutes in Group I and 92±31 minutes in Group II. The full cost of the two procedures was analyzed: the mean cost, using the O-Arm system (Group II), was found to be €255.83 (3.80%) less than the cost of Group I. Moreover, the O-Arm system was also used in other surgical procedures as an intraoperative control, thus reducing the final costs of radiologic examinations (a reduction of around 550 CT scans/year). CONCLUSIONS: In conclusion, the authors of the study are of the opinion that the surgical procedure of pedicle screw fixation, using a CT-based computer-guidance system with support of the O-Arm system, allows a shortening of procedure time that might improve the clinical result. However, the present study failed to determine a clear cost-effectiveness with respect to other CT-based IGS.