Introduction: Managed Entry Agreements (MEAs) consist of a set of instruments to reduce the uncertainty and the budget impact of new high priced medicines; however, there are concerns. There is a need to critically appraise MEAs with their planned introduction in Brazil. Accordingly, the objective is to identify and appraise key attributes and concerns with MEAs among payers and their advisers, with the findings providing critical considerations for Brazil and other high-and middle-income countries. Methods: An integrative review approach was adopted. This involved a review of MEAs across countries. The review question was 'What are the health technology MEAs that have been applied around the world?' This review was supplemented with studies not retrieved in the search known to the senior level co-authors including key South American markets. Afterall, involved senior level decision makers and advisers providing guidance on potential advantages and disadvantages of MEAs and ways forward. Results: 25 studies were included in the review. Most MEAs included medicines (96.8%), focused on financial arrangements (43%), and included mostly antineoplastic medicines. Most countries kept key information confidential including discounts or had not published such data. Few details were found in the literature regarding South America. Our findings and inputs resulted in both advantages including reimbursement and disadvantages including concerns with data collection for outcome-based schemes. Conclusion: We are likely to see a growth in MEAs with the continual launch of new high priced and often complex treatments, coupled with increasing demands on resources. Whilst outcome based MEAs could be an important tool to improve access to new innovative medicines there are critical issues to address. Comparing knowledge, experiences and practices across countries is crucial to guide high-and middle-income countries when designing their future MEAs.

Influenza is a viral respiratory disease that causes significant clinical and economic burden globally. Quadrivalent influenza vaccine (QIV) is frequently used to protect people who have a high-risk of developing influenza complications due to comorbidities. QIV offers protection against influenza A (A/ H1N1 and H3N2) and B (B/Victoria, and B/Yamagata) strains. The European Medicines Agency has recently approved a cell-based QIV (QIVc) in people aged over 9 years old. QIVc has been shown to be more effective at preventing influenza than traditional egg-based QIV (QIVe). In this study, we use a health economic model adapted to Spain to assess the costs and outcomes associated with using QIVc instead of QIVe in people aged 9-64 at high-risk of complications. Observed vaccine coverage of 32% in the 9-17 age group, 17% in those aged 18-59, and 22% for ages 60-64 was used in the analysis. In total, 2.5 million people were vaccinated in the simulations. Using QIVc instead of QIVe was associated with 16,221fewer symptomatic cases, 4,522 fewer primary care visits, 1,015 fewer emergency room visits and 88 fewer hospitalizations. From a societal perspective, QIVc was more effective and less expensive compared to QIVe, leading to a cost-saving of €3.4 million. From a public payer perspective, the incremental cost-effectiveness ratio for QIVc vs QIVe was €12,852 per QALY gained. In conclusion, QIVc offers a cost-effective alternative to QIVe and should be considered as an alternative vaccine to QIVe for people aged 9-64 at high-risk of influenza complications in Spain.

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El envejecimiento muscular puede afectar a la función oculomotora. Este estudio comparativo y correlacional muestra diferencias estadísticamente significativas en los resultados del gaze stability test entre un grupo de jóvenes y adultos, y uno de ancianos, si bien, no hay diferencias significativas entre el grupo de ancianos con cefalea y asintomáticos.

Cost-effectiveness and Burden of Disease Associated with Quadrivalent Cell-based and Egg-based Influenza Vaccines in Spain" that concludes cell-based quadrivalent influenza vaccine (QIVc) offers a cost-effective alternative to egg-based quadrivalent influenza vaccine (QIVe) and should be considered as an alternative vaccine to QIVe for people aged 9-64 at high risk of influenza complications in Spain. 1 Alvarez et al. correctly point out that the results are highly sensitive to the benefit of QIVc over QIVe and that vaccine effectiveness (VE) should ideally be based on systematic review or meta-analysis and subject to sensitivity analyses.When our economic evaluation was conducted, the study by Boikos et al. 2 (now published in a peer-review journal 3 ) was the only study of its kind. It is based on influenza-like-illness (ILI) defined through diagnosis codes and included over 60,000 patients. Alvarez et al. suggest alternative sources for metaanalyses, but these are unsuitable because: