The impact of social cohesion and risk communication on excess mortality due to COVID-19 in 213 countries: a retrospective analysis.

BACKGROUND: Tools for assessing a country's capacity in the face of public health emergencies must be reviewed, as they were not predictive of the COVID-19 pandemic. Social cohesion and risk communication, which are related to trust in government and trust in others, may have influenced adherence to government measures and mortality rates due to COVID-19. OBJECTIVE: To analyse the association between indicators of social cohesion and risk communication and COVID-19 outcomes in 213 countries. RESULTS: Social cohesion and risk communication, in their dimensions (public trust in politicians, trust in others, social safety nets, and equal distribution of resources index), were associated with lower excess mortality due to COVID-19. The number of COVID-19-related disorder events and government transparency were associated with higher excess mortality due to COVID-19. The lower the percentage of unemployed people, the higher the excess mortality due to COVID-19. Most of the social cohesion and risk communication variables were associated with better vaccination indicators, except for social capital and engaged society, which had no statistically significant association. The greater the gender equality, the better the vaccination indicators, such as the number of people who received all doses. CONCLUSION: Public trust in politicians, trust in others, equal distribution of resources and government that cares about the most vulnerable, starting with the implementation of programs, such as cash transfers and combating food insecurity, were factors that reduced the excess mortality due to COVID-19. Countries, especially those with limited resources and marked by social, economic, and health inequalities, must invest in strengthening social cohesion and risk communication, which are robust strategies to better cope with future pandemics.

Post-marketing authorisation safety and efficacy surveillance of advanced therapy medicinal products in Brazil, the European Union, the United States and Japan.

BACKGROUND AIMS: Advanced therapy medicinal products (ATMPs) are a class of biological products for human use that are based on gene, tissues or cells. ATMPs have peculiar characteristics when compared with traditional medicines. In this regard, long-term safety and efficacy follow-up systems of individuals treated with ATMPs have become necessary and may present unique challenges, because unlike conventional drugs and biologics, these products can exert their effects for years after administration. This work seeks to assess the requirements foreseen in the regulatory frameworks for the post-marketing authorization safety and efficacy surveillance for ATMPs in Brazil, European Union (EU), Japan and United States, which are some of the members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. METHODS: We reviewed the scientific literature and official documents of regulatory agencies (RAs) in Brazil, the EU, Japan and the United States. RESULTS AND CONCLUSIONS: RAs in the EU, US and Japan have developed regulatory guidelines for the post-marketing surveillance of ATMPs. These guidelines aim at implementing surveillance plans for monitoring adverse events, including late ones, after marketing authorization. All the ATMPs authorized by the RAs studied, submitted some type of post-marketing requirement to supplement safety and efficacy data, according to the regulations and terminology used by those jurisdictions.

National governance and excess mortality due to COVID-19 in 213 countries: a retrospective analysis and perspectives on future pandemics.

BACKGROUND: National governance may have influenced the response of institutions to the Covid-19 pandemic, being a key factor in preparing for the next pandemics. The objective was to analyze the association between excess mortality due to COVID-19 (daily and cumulative per 100 thousand people) and national governance indicators in 213 countries. METHOD: Multiple linear regression models using secondary data from large international datasets that are in the public domain were performed. Governance indicators corresponded to six dimensions: (i) Voice and Accountability; (ii) Political Stability and Absence of Violence/Terrorism; (iii) Government Effectiveness; (iv) Regulatory Quality; (v) Rule of Law and (vi) Control of Corruption. The statistical analysis consisted of adjusting a multiple linear regression model. Excess mortality due to COVID-19 was adjusted for potential confounding factors (demographic, environmental, health, economic, and ethnic variables). RESULTS: The indicators Control of Corruption, Government Effectiveness, Regulatory Quality and Rule of Law had a significant inverse association (p < 0.0001) with the estimated excess mortality in 2020, 2021 and 2022. Furthermore, the governance indicators had a direct significant association (p < 0.0001) with the vaccination variables (People_fully_vaccinated; Delivered population; The total number of vaccination doses administered per 100 people at the country level), except for the variables Vaccination policies and Administration of first dose, which were inversely associated. In countries with better governance, COVID-19 vaccination was initiated earlier. CONCLUSION: Better national governance indicators were associated with lower excess mortality due to COVID-19 and faster administration of the first dose of the COVID-19 vaccine.

Comparison of new Brazilian legislation for the approval of advanced therapy medicinal products with existing systems in the USA, European Union and Japan.

BACKGROUND AIMS: Advanced therapy medicinal products (ATMPs) are a class of biological products for human use that are based on genes, cells and tissues. The first ATMP received marketing authorization in Europe in 2009, whereas Brazil granted the first authorization in 2020. The objective of this study was to compare the regulatory models adopted by Brazil, the USA, Japan and the European Union, which comprise the member countries of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, with regard to the marketing authorization of ATMPs. METHODS: The authors performed a review of the scientific literature and official documents of the regulatory agencies in the aforementioned countries. RESULTS: The legislation and regulatory guidelines adopted by the regulatory agencies exhibit similarities and differences. It was not possible to assess whether these differences can be translated into divergent final recommendations by regulatory authorities upon a request for marketing authorization. CONCLUSIONS: In the future, it will be appropriate to start a progressive process of harmonization between these agencies in terms of terminology, legal recommendations and characterization requirements. This is particularly important for emerging countries such as Brazil. In this sense, some measures can be taken to achieve alignment between regulators.

The patient's safety and access to experimental drugs after the termination of clinical trials: regulations and trends.

PURPOSE: Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development. METHODS: This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database. RESULTS: Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not. CONCLUSIONS: The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

The High "Cost" of Experimental Drugs Obtained Through Health Litigation in Brazil.

BACKGROUND: Brazilian patients have legal right to access unlicensed medicines undergoing clinical research, if there is evidence of efficacy and safety. This study investigated the occurrence of serious adverse events related to very high-cost medicines from clinical studies, expanded access and compassionate use programs, obtained by patients though health litigation. METHODS: A descriptive study using secondary data investigated unlicensed medicines obtained through lawsuits from 2010 to 2017, costing more than 1 million Brazilian reais (BRL), adjusted by the Brazilian Consumer Index to July 2017. Data sources were the Brazilian Health Surveillance Agency Registry (DATAVISA) and Adverse Events in Clinical Studies (NotivisaEC) Databases. Medicines were categorized by the Anatomical Therapeutic Chemical classification to level 03 and events by the WHO Adverse Drug Reaction Terminology. The study received ethical approval by the University of Brasilia Institutional Research Board. RESULTS: In the period, 812 drugs were obtained through litigation, and of these, 78 exceeded cost of 1 million BRL; 44 of them presented reports of 1,248 serious adverse events. Total Brazilian Government expenditure with these drugs was 3.2 billion BRL. Class L04A (n=7) showed greater expenditures (over 1.8 billion BRL). One hundred ninety-six deaths occurred and L01X was the most involved category (49.5%). Most other serious events (n=419) and sequelae (n=10) were related to L01X. CONCLUSION: Very high-cost drugs paid for by the government and obtained through health litigation presented deaths and serious adverse events in expanded access and compassionate use programs in Brazil.

Research Priorities and Resource Allocation in the Investigation of New Drugs for Cancer in Least Developed Countries.

Cancer incidence has increased significantly in low- and middle-income countries. The priorities of international health research are not always aligned with the global burden of cancer. This study aims to analyze global tendencies in clinical trials in oncology and discuss research priorities and resource allocation in the investigation of new drugs for cancers that significantly affect the least developed countries. This was a retrospective and analytical study that included data collected from the World Health Organization's International Clinical Trials Registry Platform (ICTRP) in 2014. According to our results, there was a tendency for clinical trials involving breast and lung cancer to be conducted in countries with a lower level of economic development. On the other hand, cervical, stomach, and liver cancer, despite the significant burden that these place on middle- and low-income countries, were studied little among the countries selected. In conclusion, the organizations that most fund research to develop new drugs for cancer treatment continue to show little interest in prioritizing resources to fund research for certain types of cancer such as those of the cervix, stomach, and liver, which have a significant impact in low- and middle-income countries.