scholarly journals Methodological Characteristics of Clinical Trials Supporting the Marketing Authorisation of Advanced Therapies in the European Union

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolina Iglesias-Lopez ◽  
Antònia Agustí ◽  
Antonio Vallano ◽  
Merce Obach

Several advanced therapy medicinal products (ATMPs) have been approved in the European Union (EU). The aim of this study is to analyse the methodological features of the clinical trials (CT) that supported the marketing authorization (MA) of the approved ATMPs in the EU. A systematic review of the characteristics of pivotal CT of ATMPs approved in the EU until January 31st, 2021 was carried out. A total of 17 ATMPs were approved and 23 CT were conducted to support the MA (median, 1, range, 1–3). Of those studies, 8 (34.78%) were non-controlled and 7 (30.43%) used historical controls. Only 7 (30.4%) were placebo or active-controlled studies. Among all CT, 21 (91.3%) were open-label and 13 (56.52%) had a single-arm design. To evaluate the primary endpoint, 18 (78.26%) studies used an intermediate and single variable. The median (IQR) number of patients enrolled in the studies was 75 (22–118). To date, ATMPs’ approval in the EU is mainly supported by uncontrolled, single-arm pivotal CT. Although there is a trend toward an adaptive or a life cycle approach, a switch to more robust clinical trial designs is expected to better define the benefit and the therapeutic added value of ATMPs.

2021 ◽  
Vol 14 (1) ◽  
pp. 100
Author(s):  
Joanna Stawska ◽  
Małgorzata Jabłońska

The aim of the article is to identify a degree of inclusive growth and to examine the influence of determinants of inclusive growth in the European Union (EU-27) countries, with particular emphasis on factors related to the influence of governments and central banks. The study took advantage of the weight correlation method, which was used to build an inclusive growth measure for the EU-27 for the years 2000, 2008, and 2020. For the construction of the inclusive growth rate, 42 factors were selected that affect inclusive growth in the economic, financial, and non-wage area. These determinants are found in the area of the influence of economic authorities, and mainly in the area of authorities responsible for conducting monetary and fiscal policy and general governance. On the basis of the built-up indicator of inclusive growth, it was noticed that among the 27 EU countries in the studied three years, only four countries distinguished themselves with the highest inclusive growth over the last 21 years, these are: Denmark, Luxembourg, Sweden, and Finland. On the other hand, invariably, three countries recorded the lowest inclusive growth, i.e., Bulgaria, Croatia, and Romania. The added value of the structure of the inclusive growth indicator was a possibility to observe which of the three areas: economic, financial, or non-wage, had a significant impact on the position of a given country in the compiled inclusive growth ranking.


2021 ◽  
pp. 195-212

This chapter discusses the publication of the European Clinical Trials Directive in 2001 and its incorporation into the law of Member States. It explores the intention of the Directive in harmonising the rules for conducting clinical trials within the EU to facilitate the internal market in medicinal products and to protect the rights, safety, and well-being of participants. It also covers the passing of the new Clinical Trials Regulation (CTR) by the EU in 2014, which was prompted by concern that the system for approving clinical trials was overly bureaucratic and that it was hampering multinational trials. The CTR could not come into force until the Clinical Trial Information System (CTIS), which is intended to provide a single coordinated approval process, became fully functional. This happened too late for the CTR to be automatically incorporated into UK law by the European Union (Withdrawal) Act 2018.


Author(s):  
E. Siemers

In October 2018, the European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) met to discuss an increasingly important topic, the scientific, regulatory, and logistical challenges to the development of combination therapies for AD. Challenges related to ever-changing scientific knowledge, challenges related to complex regulatory pathways and challenges related to the necessity for pharmaceutical companies to collaborate must all be addressed. These challenges must be met since task Force members unanimously agreed that successful treatment of AD will likely require combination therapies targeting multiple mechanisms and pathways.


Author(s):  
Ryosuke Kurauchi ◽  
Hiroi Kasai ◽  
Tatsuya Ito

Medical products comprising human cells, genes, and tissues have been developed for clinical applications worldwide, and their developmental environment has been established. These products can be imported and exported, but marketing authorization regulations are complicated among regions. This investigation was conducted to identify the characteristics of medical products comprising human cells, genes, and tissues. We used website data, books from survey companies, and reports from public agencies to conduct two investigations. We used website data to conduct a general information survey of 143 cell-therapy and gene-therapy products sold in 24 countries and public assessment reports to individually survey non-clinical and clinical developments of 18 cell-therapy and gene-therapy products developed in Japan and the European Union (EU). The first survey revealed that the numbers of products used in orthopedic surgery and dermatology have increased since 2000, and the numbers of hematological products have increased since 2011. The second investigation revealed that fewer orphaned products were developed in Japan than in the EU. The most appropriate dose was 1.2 × 108 cells per injection per adult. Clinical trials to determine the most appropriate dose were conducted in the EU but not in Japan. No non-clinical immunogenicity tests for autogenous products were conducted in Japan or the EU. Pharmacokinetics tests were not individually performed for sheet-form products. Both in vivo and in vitro pharmacological tests were more likely to be conducted in the EU, while only one or the other was conducted in Japan. Furthermore, in Japan, carcinogenicity tests were performed based on non-clinical technical guidance, while in the EU, these tests were determined according to each product's features. Fewer clinical trials were performed, and fewer subjects per product were used in Japan than in the EU. Many aspects of the clinical and non-clinical development of medical products comprising human cells, genes, and tissues differ between Japan and the EU. Analyzing these differences will enable the safe and rapid distribution of these products to clinical sites.


Author(s):  
Simona Piattoni ◽  
Laura Polverari

Cohesion policy is one of the longest-standing features of the European construction; its roots have been traced as far back as the Treaty of Rome. Over time, it has become one of the most politically salient and sizable policies of the European Union, absorbing approximately one-third of the EU budget. Given its principles and “shared management” approach, it mobilizes many different actors at multiple territorial scales, and by promoting “territorial cooperation” it has encouraged public authorities to work together, thus overcoming national borders. Furthermore, cohesion policy is commonly considered the most significant expression of solidarity between member states and the most tangible way in which EU citizens “experience” the European Union. While retaining its overarching mission of supporting lagging regions and encouraging the harmonious development of the Union, cohesion policy has steadily evolved and adapted in response to new internal and external challenges, such as those generated by subsequent rounds of enlargement, globalization, and shifting political preferences regarding what the EU should be about. Just as the policy has evolved over time in terms of its shape and priorities, so have the theoretical understandings of economic development that underpin its logic, the nature of intergovernmental relations, and the geographical and administrative space(s) within which the EU polity operates. For example, whereas overcoming the physical barriers to economic development were the initial targets in the 1960s and 1970s, and redesigning manufacturing clusters were those of the 1980s and 1990s, fostering advanced knowledge and technological progress became the focus of cohesion policy in the new century. At the same time, cohesion policy also inspired or even became a testing ground for new theories, such as multilevel governance, Europeanization, or smart specialization. Given its redistributive nature, debates have proliferated around its impact, added value, and administrative cost, as well as the institutional characteristics that it requires to function. These deliberations have, in turn, informed the policy in its periodic transformations. Political factors have also played a key role in shaping the evolution of the policy. Each reform has been closely linked to the debates on the European budget, where the net positions of member states have tended to dominate the agenda. An outcome of this process has been the progressive alignment with wider strategic goals beyond cohesion and convergence and the strengthening of linkages with the European Semester. However, some argue that policymakers have failed to properly consider the perverse effects of austerity on regional disparities. These unresolved tensions are particularly significant in a context denoted by a rise of populist and nativist movements, increasing social discontent, and strengthening Euroskepticism. As highlighted by research on its communication, cohesion policy may well be the answer for winning back the hearts and minds of European citizens. Whether and how this may be achieved will likely be the focus of research in the years ahead.


Atlanti ◽  
2016 ◽  
Vol 26 (2) ◽  
pp. 59-64
Author(s):  
Dieter Schlenker

The Historical Archives of the European Union (HAEU) is a centre dedicated to the archival preservation and research on the history of European integration. In close cooperation with the Archives services of the EU Institutions, the HAEU preserves and make available to research the archival holdings of EU Institutions. Also, the Archives promotes research on the history of the EU Institutions, raises the public interest in the process of European integration and increases transparency in the EU Institutions’ work. Established following a decision by the European Communities in 1983 to open their historical archives to the public, the HAEU opened its doors in 1986. As part of the European University Institute, it is located in the historic Villa Salviati in Florence, Italy. The internet era and the modern information society have profoundly changed the research behaviour at the HAEU, in particular due to its unique character as transnational and multi-lingual archives. As central access point to EU institutional archives it is part of a network of more than 50 EU Institutions, Bodies and Agencies and seeks to respond, in close collaboration with its partners, to the challenges of the digital age. This paper outlines some key projects in terms of coping with research in an online archival database, the necessity to standardise and harmonise archival description, the added value of standardised vocabularies and the digitisation and online publication of paper archives.


Author(s):  
Olimpia Neagu ◽  
Florin Dumiter ◽  
Alexandra Braica ◽  
Ștefania Jimon ◽  
Gabriela David

Abstract The paper aims to prove the link between human capital and gross added value in bioeconomy sectors in the EU countries. Data from EUROSTAT data base regarding employment and gross added value in 6 bioeconomy sectors were used in a cross-country regression analysis. The econometric analysis of cross-country data shows a positive correlation between human capital in bioeconomy sectors and their gross output in 2015 in 26 European countries. It is found also that the correlation is stronger in the highly developed economies as in the central-eastern countries, as well as in the European economy.


Author(s):  
Mikołaj Bartoszkiewicz ◽  
Joanna Kufel-Grabowska ◽  
Maria Litwiniuk

Introduction: The clinical research market of the European Union (EU) countries of Central and Eastern Europe has been experiencing a dynamic growth of clinical trials in the last 10 years. Oncology and cardiology are the areas where the most clinical trials are conducted. Aim: This study aims to analyze the clinical research market including countries, medical fields and trial phases in the EU countries of Central and Eastern Europe. The comparative analysis of countries is divided into 5-year periods. Material and methods: Clinical research market analysis was carried out in 11 EU countries of Central and Eastern Europe: Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia. In searching for the number of clinical trials, the ClinicalTrials.gov database was used. Results and discussion: From 2000 to 2019, 6497 clinical trials were conducted in the EU countries of Central and Eastern Europe. There were 1840 clinical trials registered in Poland, 1188 in Czechia, and 1005 in Hungary. The most clinical trials were registered in the field of oncology (22%), followed by cardiology (16%) and neurology (12%). Phase III trials representing as much as 60% (n = 2854) of all conducted medical experiments. The highest increase in the number of clinical trials in the last two 5-year periods (2010–2014 and 2015–2019) was recorded in Estonia, at 471%. Conclusions: There has been a significant increase in the number of clinical phase III trials in the EU countries of Central and Eastern Europe, mainly in Poland, Czechia, and Hungary.


Author(s):  
S. Gauthier ◽  
J. Alam ◽  
H. Fillit ◽  
T. Iwatsubo ◽  
H. Liu-Seifert ◽  
...  

Combination therapy is expected to play an important role for the treatment of Alzheimer’s disease (AD). In October 2018, the European Union-North American Clinical Trials in Alzheimer’s Disease Task Force (EU/US CTAD Task Force) met to discuss scientific, regulatory, and logistical challenges to the development of combination therapy for AD and current efforts to address these challenges. Task Force members unanimously agreed that successful treatment of AD will likely require combination therapy approaches that target multiple mechanisms and pathways. They further agreed on the need for global collaboration and sharing of data and resources to accelerate development of such approaches.


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