Marketing Authorization Applications Made to the European Medicines Agency in 2018-2019: What was the Contribution of Real-World Evidence?

Information derived from routinely collected real-world data has for a long time been used to support regulatory decision making on the safety of drugs and has more recently been used to support marketing authorization submissions to regulators. There is a lack of detailed information on the use and types of this real-world evidence (RWE) as submitted to regulators. We used resources held by the European Medicines Agency (EMA) to describe the characteristics of RWE included in new marketing authorization applications (MAAs) and extensions of indication (EOIs) for already authorized products submitted to the EMA in 2018 and 2019. For MAAs, 63 of 158 products (39.9%) contained RWE with a total of 117 studies. For 31.7% of these products, the RWE submitted was derived from data collected before the planned authorization. The most common data sources were registries (60.3%) followed by hospital data (31.7%). RWE was mainly included to support safety (87.3%) and efficacy (49.2%) with cohort studies being the most frequently used study design (88.9%). For EOIs, 28 of 153 products (18.3%) contained RWE with a total of 36 studies. For 57.1% of these products, studies were conducted prior to the EOIs. RWE sources were mainly registries (35.6%) and hospital data (27.0%). RWE was typically used to support safety (82.1%) and efficacy (53.6%). Cohort studies were the most commonly used study design (87.6%). We conclude that there is widespread use of RWE to support evaluation of MAAs and EOIs submitted to the EMA and identify areas where further research is required.

Implementation of a pharmacogenomic program in a Brazilian public institution.

This narrative review describes implementation, current status and perspectives of a pharmacogenomic (PGx) program at the Brazilian National Cancer Institute (INCA), targeting the cancer chemotherapeutic drugs - fluoropyrimidines, irinotecan and thiopurines. This initiative, designed as a research project, was supported by a grant from the Brazilian Ministry of Health. A dedicated task force developed standard operational procedures from recruitment of patients to creating PGx reports with dosing recommendations, which were successfully applied to test 100 gastrointestinal cancer INCA outpatients and 162 acute lymphoblastic leukemia pediatric patients from INCA and seven other hospitals. The program has been subsequently expanded to include gastrointestinal cancer patients from three additional cancer treatment centers. We anticipate implementation of routine pre-emptive PGx testing at INCA but acknowledge challenges associated with this transition, such as continuous financing support, availability of trained personnel, adoption of the PGx-informed prescription by the clinical staff and, ultimately, evidence of cost-effectiveness.

Promoting the One Health concept: Thai Coordinating Unit for One Health.

Within the last decade, One Health has gained momentum in government agencies, academic institutions, intergovernmental organisations and civil society organisations within Thailand. One Health is an approach of multisectoral and multidisciplinary collaboration that connects human, animal and environmental health sectors to improve the health of all. In 2014, the Coordinating Unit for One Health (CUOH), based within the Thai Ministry of Public Health, was officially established to serve as a focal point within Thailand for One Health collaboration both domestically and internationally. The unit's main functions are to share data, information and resources, and to support One Health activities within the country. The CUOH Steering Committee meets regularly to provide technical and administrative guidance on the functions and directions of the CUOH. A memorandum of understanding on One Health, signed in 2016 by seven Ministries and the Thai Red Cross Society, has strengthened One Health collaboration and provides a formalised channel through which the CUOH can facilitate activities across Ministries and with non-governmental agencies in Thailand.

En l'espace d'une décennie, le recours aux méthodes Une seule santé en Thaïlande s'est intensifié au sein des agences gouvernementales, des institutions académiques, des organisations intergouvernementales et des organisations de la société civile. La collaboration multisectorielle et pluridisciplinaire mise en place selon les principes Une seule santé vise à connecter les secteurs de la santé publique, la santé animale et la santé environnementale afin d'améliorer la santé pour tous. En 2014, l'Unité de coordination Une seule santé (CUOH) a été officiellement créée au sein du ministère thaïlandais de la santé publique dans le but de servir de point focal national pour la collaboration Une seule santé aussi bien dans le pays qu'au niveau international. L'Unité a pour principales fonctions le partage de données, d'informations et de ressources et le soutien aux activités Une seule santé dans le pays. Le comité directeur de la CUOH se réunit régulièrement pour fixer les orientations techniques et administratives des tâches et des objectifs de l'Unité. Un protocole d'accord sur le thème Une seule santé signé en 2016 par sept ministères et la Société thaïlandaise de la Croix rouge renforce cette collaboration Une seule santé et fournit un canal officiel grâce auquel la CUOH peut déployer des activités transversales faisant intervenir plusieurs ministères et organisations non gouvernementales en Thaïlande.

En el curso del último decenio, la noción de Una sola salud ha ido ganando presencia y peso en el seno de organismos públicos, instituciones universitarias, organizaciones intergubernamentales y entidades de la sociedad civil de Tailandia. La filosofía de Una sola salud se traduce en un trabajo de colaboración multisectorial y pluridisciplinar que conecta entre sí los sectores de la salud humana, animal y ambiental con el objetivo último de hacer realidad un mejor estado de salud para todos. En 2014 se estableció oficialmente dentro del Ministerio de Salud Pública de Tailandia la Unidad de Coordinación en pro de Una sola salud, que tiene por cometido ejercer de enlace dentro del país de todas las actividades de colaboración en clave de Una sola salud, ya sean nacionales o internacionales. Sus principales funciones son el intercambio de datos, información y recursos y la prestación de apoyo a dichas actividades dentro del país. Su Comité de Dirección se reúne periódicamente para marcar pautas técnicas y administrativas sobre las funciones y las líneas de trabajo de la Unidad. En 2016, siete ministerios y la Sociedad Tailandesa de la Cruz Roja suscribieron un memorando de entendimiento en torno a la noción de Una sola salud que, además de reforzar la colaboración encuadrada en esta filosofía, abre un cauce oficial a través del cual la Unidad puede facilitar el trabajo interministerial o la colaboración con entidades no gubernamentales en Tailandia.

Flexible and Expedited Regulatory Review Processes for Innovative Medicines and Regenerative Medical Products in the US, the EU, and Japan.

Several expedited regulatory review projects for innovative drugs and regenerative medical products have been developed in the US, the EU, and Japan. Each regulatory agency has elaborated an original regulatory framework and adopted regulatory projects developed by the other regulatory agencies. For example, the Food and Drug Administration (FDA) first developed the breakthrough therapy designation, and then the Pharmaceuticals and Medical Devices Agency (PMDA) and European Medicines Agency (EMA) introduced the Sakigake designation and the priority medicines (PRIME) designation, respectively. In addition, the necessity of the product being first development in Japan is the original feature of the Sakigake designation, while actively supporting the development of advanced-therapy medicinal products (AMTPs) by academia or small/medium-sized sponsors is the original feature of the PRIME; these particular features are different from the breakthrough therapy designation in the US. In this review article, flexible and expedited review processes for new drugs, and cell and gene therapies in the US, the EU, and Japan are described. Moreover, all the drugs and regenerative medical products that were granted conditional approval or Sakigake designation in Japan are listed and analyzed herein.

A neo-institutional analysis of the hidden interaction between the Israeli Supreme Court and the Ministry of Finance: the right to healthcare services.

BACKGROUND: Under structural conditions of non-governability, most players in the policy arena in Israel turn to two main channels that have proven effective in promoting the policies they seek: the submission of petitions to the High Court of Justice and making legislative amendments through the Economic Arrangements Law initiated by the Ministry of Finance. Nevertheless, an analysis of the principal trends emerging from the High Court of Justice rulings and legislative amendments through the Economic Arrangements Law indicates that these channels are open to influence, primarily by forces that are essentially neo-liberal. Little is known about the effects of these trends on the right to healthcare services, which in Israel has not been legislated as an independent constitutional law in Basic Laws. METHODS: We use four major legal cases decided by the Supreme Court of Israel in the past 10 years where the Court reviewed new legislative initiatives proposed by the Economic Arrangements Law in the area of healthcare. We utilize an institutional approach in our analysis. RESULTS: A neo-institutional analysis of the legal cases demonstrates that petitions against the Economic Arrangements Law in the area of healthcare services have been denied, even though the Court uses strong rhetoric against that law and the government more generally in addressing issues that concern access to healthcare services and reforms in the healthcare system. This move strengthens the trend toward a neo-liberal public policy and significantly weakens the legal protection of the right to healthcare services. CONCLUSION: In deciding petitions against the Economic Arrangements Law in the area of healthcare, the Supreme Court allows the Ministry of Finance to be a dominant player in the formation of public policy. In doing so, it may be promoting a goal of strengthening its position as a political institution that aspires to increase the public's trust in the judiciary and especially in the Supreme Court itself, in addition to exercising judicial restraint and allowing more leeway to the executive and legislative branches more generally.

Building Synergy between Regulatory and HTA Agencies beyond Processes and Procedures-Can We Effectively Align the Evidentiary Requirements? A Survey of Stakeholder Perceptions.

OBJECTIVES: To evaluate the current practice of companies and agencies to assess the changes made in aligning regulatory and health technology assessment (HTA) stakeholders; to identify areas of commonality of evidentiary requirements that could occur; and to identify strategic issues and trends of regulatory and HTA synergy. METHODS: Two separate questionnaires were developed to assess stakeholders' perceptions on regulatory and HTA alignment, one for pharmaceutical companies and the other for regulatory and HTA agencies. The responses were analyzed using descriptive statistics. RESULTS: Seven regulatory and 8 HTA agencies from Australia, Canada, and Europe and 19 international companies developing innovative medicine responded to the survey. This study provided a snapshot of the current regulatory and HTA landscape. Changes made over the past 5 years were reflected in three main areas: there is an increasing interaction between regulatory and HTA agencies; current conditional regulatory approvals are not always linked with flexible HTA approaches; and companies are more supportive of joint scientific advice. Four types of evidentiary requirements were identified as building blocks for better alignment: acceptable primary end points, inclusion of an active comparator, use of patient-reported outcomes, and choice and use of surrogate end point. CONCLUSIONS: The study showed that the gap between regulatory and HTA requirements has narrowed over the past 5 years. All respondents supported synergy between regulatory and HTA stakeholders, and the study provided several recommendations on how to further improve evidentiary alignment including the provision of joint scientific advice, which was rated as a key strategy by both agencies and companies.

The Taiwan Tobacco and Liquor Corporation: To 'join the ranks of global companies'.

Until the late 1990s, the Taiwan Tobacco and Liquor Corporation (TTL) focused almost exclusively on serving the domestic market as a highly protected monopoly. This paper describes how the company has adopted a more outward looking strategy since 2000, with ambitions to become a regional, and eventually global, business by 2021. Drawing on company documents and industry sources, the paper argues that this shift in strategy was a direct reaction to the decline in domestic market share following liberalisation of the Taiwanese tobacco market and adoption of tougher domestic tobacco control measures. Market opening occurred as a result of pressure from the U.S. Trade Representative in the 1980s, as well as World Trade Organization membership in 2002. It is argued that TTL's efforts to globalise operations have been limited by bureaucratic company management and structures, and ongoing political tension between Taiwan and China. However, the relative success of TTL's alcohol branch, and potential détente as the Taiwanese government reaches out to improve relations with China, may provide TTL with new opportunities to achieve its goal of becoming a regional player with global ambitions. This article is part of the special issue 'The Emergence of Asian Tobacco Companies: Implications for Global Health Governance.'

A Multiagency Approach to Reducing West Nile Virus Risk in Richmond County, Georgia, in 2015.

The Richmond County Mosquito Control program's mission statement is to incorporate strategies of integrated mosquito control management that are effective, practical, and environmentally safe and protect the health of Richmond County residents, as well as promote public education, in order to prevent large mosquito populations and the diseases that they transmit. To this end, the program coordinates efforts with other county agencies in order to provide better service. This is a small program with limited resources, so in an effort to provide better integrated mosquito management, the mosquito control program and the Phinizy Center for Water Sciences joined efforts to trap mosquitoes at sites across the county, identify the species, and send the mosquitoes off for viral testing. These data help determine locations of disease-carrying mosquitoes so the county can more efficiently control the mosquito populations and reduce the risk of West Nile virus transmission.

HEALTH CARE ECONOMICS IN ROMANIA--DYNAMICS AND EVOLUTION.

Health economics refers to the analysis of medical institutions considering their economic and social efficacy, but also the regularity and the relationships that govern the phenomena and the processes from the field of health with the final purpose of achieving better results with the minimum of resources; it represents the study of health price in its complexity. The economics of the population's health needs and in particular the health needs in case of the poor groups of the population, consider health to be the main component of global human vulnerability. Health economics tries to change the simple interpretation of health price and disease cost into a wider consideration of a system administration similar to educational and social economics and the study of health in the context of the multiple specializations of the macro economy of the national group, as it is an instrument in the country's great economics symphony.