Implications of EMU enlargement for European monetary policy: A political economy view

EU Enlargement, Economic Convergence, Political Economy

Corporate finance in the euro area – including background material

This report analyses the financial position of non-financial enterprises in the euro area, in particular the amount of external financing, the choice between debt and equity and the composition and maturity structure of debt. It aims at identifying the main features of the euro area, as well as the peculiarities that depend on the country of origin and the sector of activity. Attention is also devoted to assessing whether a country’s institutional eatures are correlated with different financial structures by firms. In light of the particular interest in the access of small and medium-sized enterprises (SMEs) to financing, the report also analyses how financing patterns differ across large, medium-sized and small enterprises. Finally, the report discusses the recent trends observed in the corporate finance landscape of the euro area over the past few years. Although it is still too early to pass final judgement, vast structural changes are underway that could have already influenced in a positive way in the availability of external funds for firms. All in all, a comprehensive understanding of corporate finance in the euro area is important from a monetary policy perspective, given its impact on the transmission mechanism and for productivity and economic growth. Moreover, such an understanding is also relevant from a financial stability perspective. A first assessment is now possible eight years into the third stage of Economic and Monetary Union (EMU), given that sufficient data have been accumulated during this period. This assessment is particularly important as the introduction of the single currency has had significant structural effects on the working of financial markets, increasing their size and liquidity, and fostering cross-border competition. The data available for this report generally cover the period 1995-2005, and the cut-off date for the statistics included is 10 March 2007.

An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase. Objective: We propose two alternative dosing regimens for subcutaneous atezolizumab to reduce drug expenses while ensuring effective exposure; one may be directly implemented in the clinic. Patients and Methods: We developed two alternative dose interval prolongation strategies based on pharmacokinetic modeling and simulation. The first dosing regimen was based on patients’ weight while maintaining equivalent systemic drug exposure by adhering to Food and Drug Administration (FDA) guidelines for in silico dose adjustments. The second dosing regimen aimed to have a minimum atezolizumab concentration above the 6 µg/mL threshold, associated with 95% intratumoral PD-L1 receptor saturation for at least 95% of all patients. Results: We found that, for the weight-based dosing regimen, the approved 3-week dosing interval could be extended to 5 weeks for patients &lt; 50 kg and 4 weeks for patients weighing 50–65 kg. Besides improving patient convenience, these alternative dosing intervals led to a predicted 7% and 12% cost reduction for either the USA or European population. For the second dosing regimen, we predicted that a 6-week dosing interval would result in 95% of the patients above the 6 µg/mL threshold while reducing costs by 50%. Conclusions: We have developed and evaluated two alternative dosing regimens that resulted in a cost reduction. Our weight-based dosing regimen can be directly implemented and complies with FDA guidelines for alternative dosing regimens of PD-L1 inhibitors. For the more progressive alternative dosing regimen aimed at the intratumoral PD-L1 receptor threshold, further evidence on efficacy and safety is needed before implementation.</p

A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer

Background: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide. Objective: We aimed to develop alternative dosing regimens to reduce drug expenses. Methods: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan. The alternative dosing regimens were developed by means of modeling and simulation based on the population pharmacokinetic models developed by the license holders. They were based on weight bands and the administration of complete vials to limit drug wastage. The resulting dosing regimens were developed to comply with criteria used by regulatory authorities for in silico dose development. Results: We found that alternative dosing regimens could result in cost savings that range from 11 to 28%, and lead to equivalent pharmacokinetic exposure with no relevant increases in variability in exposure. Conclusions: Dosing regimens based on weight bands and the use of complete vials to reduce drug wastage result in less expenses while maintaining equivalent exposure. The level of evidence of our proposal is the same as accepted by regulatory authorities for the approval of alternative dosing regimens of other monoclonal antibodies in oncology. The proposed alternative dosing regimens can, therefore, be directly implemented in clinical practice.</p

Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study

Background: The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes. Methods: LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January–December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien–Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141). Results: A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively. Conclusions: This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives

Implications of EMU Enlargement for European Monetary Policy: A Political Economy View

In this paper we investigate the implications of EMU enlargement from a political economy perspective. We argue that a high degree of convergence of the candidate countries prior to EMU accession is an important requisite. Otherwise, as a result of a sharp increase in economic dispersion, public support for European monetary policy is likely to decrease, and external pressure on the European Central Bank will mount. (JEL E 58, E 50, D 78

Implications of EMU Enlargement for European Monetary Policy: A Political Economy View

In this paper we investigate the implications of EMU enlargement from a political economy perspective. We argue that a high degree of convergence of the candidate countries prior to EMU accession is an important req-uisite. Otherwise, as a result of a sharp increase in economic dispersion, public support for European monetary policy is likely to decrease, and external pressure on the European Central Bank will mount.EU Enlargement; Economic Convergence; Political Economy

Prostate cancer localization by contrast-ultrasound diffusion imaging

Prostate cancer is the form of cancer with the highest incidence in men. The invasiveness or low specificity of available diagnostics hampers a timely use of efficient focal therapies. New imaging techniques are therefore needed for an early prostate cancer localization. We propose a new ultrasound imaging method for prostate cancer localization based on quantification of the (intravascular) local diffusion of ultrasound contrast agents. Local diffusion is expected to correlate better than perfusion with cancer microvascular growth and, therefore, aggressiveness. Local diffusion is estimated by transrectal ultrasound imaging of an ultrasound contrast-agent bolus passing through the prostate circulation after a peripheral intravenous injection. A time-intensity curve (TIC) is measured at each pixel by acoustic quantification. The measured TICs are fitted by a modified Local Density Random Walk model, a solution of the convective diffusion equation that provides a physical representation of the diffusion process. The obtained parametric diffusion images were compared with the histology results after radical prostatectomy. The resulting receiver operating characteristics (curve area = 0.91) were superior to those obtained by estimation of perfusion related parameters. Although extensive validation is necessary, contrast ultrasound diffusion imaging is a promising method, with potential to assess cancer aggressiveness

Localization of prostate cancer by contrast-ultrasound diffusion imaging

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