Ruxandra Draghia-Akli

Toward an International Initiative for Traumatic Brain Injury Research

The European Commission (EC) and the National Institutes of Health (NIH) jointly sponsored a workshop on October 18-20, 2011 in Brussels to discuss the feasibility and benefits of an international collaboration in the field of traumatic brain injury (TBI) research. The workshop brought together scientists, clinicians, patients, and industry representatives from around the globe as well as funding agencies from the EU, Spain, the United States, and Canada. Sessions tackled both the possible goals and governance of a future initiative and the scientific questions that would most benefit from an integrated international effort: how to optimize data collection and sharing; injury classification; outcome measures; clinical study design; and statistical analysis. There was a clear consensus that increased dialogue and coordination of research at an international level would be beneficial for advancing TBI research, treatment, and care. To this end, the EC, the NIH, and the Canadian Institutes of Health Research expressed interest in developing a framework for an international initiative for TBI Research (InTBIR). The workshop participants recommended that InTBIR initially focus on collecting, standardizing, and sharing clinical TBI data for comparative effectiveness research, which will ultimately result in better management and treatments for TBI.

Gene and Cell Therapy Funding Opportunities in Horizon 2020: An Overview for 2014–2015

Since 1984, the European Commission has undertaken seven framework programs (FPs), dedicated to research and innovation, that ran for 5–7-year periods. During the fifth, sixth, and seventh FPs, more than €351 million has been invested in 110 projects in the gene transfer and gene therapy field (Table 1). While in FP5 and FP6, support was allocated mostly to small projects addressing specific problems such as refining targeted gene delivery or transgene expression in specific cells, the large-scale collaborative projects of FP6 and FP7 brought this research field from bench to bedside by gathering the critical mass of scientific expertise. Table 1. European Union Support to Gene Transfer and Gene Therapy Projects Over the Yearsa Presently, 15 FP7 gene therapy projects include clinical trials mostly for patients suffering from a rare disease or cancer, but also from more frequent disorders such as severe fetal growth restriction or age-related macular degeneration. Some of those projects (as well as their participants) derive directly from research and technologies developed in previous FPs. For example, the projects Cell-PID, performing clinical trials for primary immunodeficiencies (PIDs), and SUPERSIST, developing scale-up production of targeted genetic correction of hematopoietic stem cells and T cells for PIDs and leukemia, both derive from former FP7 PERSIST (refinement of gene therapy vectors for persisting transgenesis) and FP6 CONSERT (safety and efficiency evaluation of retroviral transgenesis) collaborative projects (ec.europa.eu/research/health/biotechnology/new-therapies/projects-fp7-gt_en.html). The specificity of these collaborative grants lies in gathering international expertise in various research disciplines, from scale-up and good manufacturing practice, development of new preclinical models, and toxicology and monitoring tests to regulatory and ethical issues of clinical trials. The eighth research and innovation program, Horizon 2020 (2014–2020), is conceived as one of the central means to drive economic growth and job creation by addressing the entire innovation cycle, from basic research to implementation. In structure, Horizon 2020 has three main pillars: excellence in science, industrial leadership, and societal challenges. The challenge addressing primarily health research under the new program will have a slightly larger budget, €7.4 bn, compared with previous programs (€2.65 bn in FP6 and €6.2 bn in FP7). The first calls for societal challenges of “health, demographic change, and wellbeing” are published. Applicants are expected to focus on problem solving, and therefore gene and cell therapy projects could find funding opportunities in topics advertising chronic or rare disease research as well as regenerative medicine or advanced therapies (Table 2). Table 2. Selection of Horizon 2020 Funding Opportunities for Gene and Cell Therapy Projects The topic “clinical research on regenerative medicine” will be open for 2 years, providing sequential or iterative opportunities to proposals ready to test in the clinic new regenerative applications. The field has considerably developed during recent years and is now ripe for clinical challenges. The topics on rare diseases (one in 2014, two in 2015) will support the general objectives of the International Rare Diseases Research Consortium (IRDiRC), initially established by the European Commission and the U.S. National Institutes for Health Research in 2011. The consortium aims at developing 200 new therapies and the means to diagnose most rare diseases by 2020. The challenges at stake are too ambitious for any country to master alone; therefore, IRDiRC now counts more than 35 funding members from four continents (www.irdirc.org/). Included in the same call, a support action for European reference networks promotes cross-border cooperation among member states. These networks are meant to improve access to and provision of high-quality specialized health care to patients and to act as focal points for medical training and research and information dissemination and evaluation, especially for rare diseases. The topics “tools and technologies for advanced therapies” and “therapies for chronic noncommunicable diseases” offer as well interesting opportunities for innovation in the gene and cell therapy field. Moreover, the first pillar of Horizon 2020 offers opportunities for frontier research science via its European Research Council grants (erc.europa.eu/funding-and-grants), for international training via its Marie Sklodowska-Curie actions (ec.europa.eu/programmes/horizon2020/en/h2020-section/marie-sk%C5%82odowska-curie-actions) and for development of international infrastructure platforms (which explicitly mention the rare disease research) and key enabling technologies. The second pillar will ensure support to research and innovation performers, including significant, tailored support to small and medium-sized enterprises for which a dedicated instrument has been developed (ec.europa.eu/research/participants/portal/desktop/en/opportunities/h2020/index.html). This is complementary to the Innovative Medicines Initiative (IMI; www.imi.europa.eu), Europes largest public–private partnership between the Commission and the European Federation of Pharmaceutical Industries and Associations aiming at promoting the development of new, improved diagnostics and therapies for patients. A renewed IMI with a budget of €3.5 bn is forecasted for the period 2014–2020. More than ever, the European Union offers to the gene and cell therapy sector possibilities of financial support to bright and innovative consortia ready to develop, possibly in collaboration with the industry, new therapeutic applications to be tested in clinical trials or novel products for the market, and build sustainable networks of expertise in the field. Recently, the first human gene therapy product in Europe, Glybera, entered the market (www.uniqure.com/products/glybera). It constitutes one of the four advanced therapy medicinal products approved by the European Medicine Agency since 2009 (www.uniqure.com/news/167/182/uniQure-s-Glybera-First-Gene-Therapy-Approved-by-European-Commission.html). Clearly, the field benefits, after a long period of stagnation, from renewed interest from academic and industrial stakeholders, including big pharma, and will witness exciting developments in the near future.

Introduction: Gene Therapy and Gene Transfer Projects of the 7th Framework Programme for Research and Technological Development of the European Union (Second Part)

We present hereafter the second opus of 12 ongoing gene therapy/gene transfer projects funded by the European Union during the 7th Framework Programme for Research and Innovation (2007–2013). Half of these projects address rare diseases (EuroFancolen, MeuSIX, Net4CGD, Scope-DMD, Skip-NMD, SUPERSIST, Thalamoss), while others investigate common disorders such as cancer (ATECT, ATTACK, SUPERSIST, MERIT), age-related macular degeneration (TargetAMD), or vascular disorders (EVERREST). Most of these international collaborative projects will perform clinical trials, demonstrating that the field is now ripe for moving to the bedside. Each project presentation includes main findings and publications in addition to their dedicated website where details about consortium’s structure and achievements can be found. Gene therapy trials and genetic engineering technologies are now regularly highlighted in the scientific news. The spectacular results obtained with the chimeric antigen receptor (CAR) T cell technology for the treatment of CD19 + B cell leukaemias and the safety evidence of new generation of viral vectors led the experts in the field to propose gene therapy as first-line treatment for some rare diseases during the last annual conference of the European Society for Gene and Cell Therapy. Moreover, the dynamism for search of innovative therapeutic modalities is exemplified within the International Rare Diseases Research Consortium (IRDiRC) that has already now delivered more than 140 new therapies for rare diseases, on the target objective of 200 by 2020. Gene and cell technologies are more complementary than ever with the development of nonviral vectors as specific tools for genetic engineering and the generation of induced pluripotent stem cell lines as potential candidates in regenerative medicine. The Innovative Medicine Initiative, a public–private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations, is supporting the generation, the characterization, and the banking of those cell lines via two projects, StemBANCC and EBiSC. The growing investments of the pharmaceutical industry in the area of new gene and cell technologies suggest that the field is now ripe for human trials.

Enabling personalized medicine in Europe: a look at the European Commission’s funding activities in the field of personalized medicine research

The potential benefits that personalized medicine approaches can bring to healthcare are discussed with much interest throughout the EU. This novel approach is based on a better understanding of the molecular mechanisms of health and disease and it has now begun to show results. There is, however, a long way to go before the area is fully exploited. This special report reviews the European Commissions funding activities related to personalized medicine research. Although the specific focus on personalized medicine is relatively new, the European Commission has already committed significant funding to research in enabling technologies relevant to the field, as well as to specific disease areas for their application. A stocktaking exercise which started in 2010 has helped identify immediate and future challenges in personalized medicine research. The outcome of this exercise, summarized below, will contribute to developing a vision for future research funding at the EU level.

European Union research in support of environment and health: Building scientific evidence base for policy

Opinion polls show that the European Union citizens are increasingly concerned about the impact of environmental factors on their health. In order to respond and provide solid scientific evidence for the numerous policies related to the protection of human health and the environment managed at the Union level, the European Union made a substantial investment in research and innovation in the past two decades through its Framework Programmes for Research and Technological Development, including the current programme, Horizon 2020, which started in 2014. This policy review paper analysed the portfolio of forty collaborative projects relevant to environment and health, which received a total amount of around 228 million euros from the EU. It gives details on their contents and general scientific trends observed, the profiles of the participating countries and institutions, and the potential policy implications of the results obtained. The increasing knowledge base is needed to make informed policy decisions in Europe and beyond, and should be useful to many stakeholders including the scientific community and regulatory authorities.

The need for innovation and implementation research for maternal and newborn health

1 WHO, UNICEF, UNFPA, World Bank Group, UN Population Division. Trends in maternal mortality: 1990 to 2015: estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division. Geneva: WHO, 2015. 2 UN Population Fund. Family planning; overview. http://www.unfpa.org/familyplanning (accessed Aug 12, 2016). 3 WHO. Neonatal mortality; situation and trends. http://www.who.int/gho/child_health/ mortality/neonatal_text/en/ (accessed Aug 12, 2016). 4 Temmerman M, Khosla R, Bhutta ZA, Bustreo F. Towards a new Global Strategy for Women’s, Children’s and Adolescents’ Health. BMJ 2015; 351: h4414. 5 Research & Innovation Horizon Prizes. Birth Day Prize. http://ec.europa.eu/research/ horizonprize/index.cfm?prize=birthday (accessed Aug 12, 2016). Inequity is a key factor to consider in MNH research, particularly regarding adolescents and migrants. Innovative approaches are needed to ensure quality of care for adolescents for whom few specialised services are available, and for the large numbers of migrants with a documented lack of access to health services. The development of effective, innovative solutions requires collaboration between academic researchers from diff erent disciplines, scientists, clinicians, and—perhaps m o s t i m p o r t a n t l y — w o m e n , their families, and communities. The involvement of end users in identifying problems and solutions provides vital insights and increases the likelihood that solutions will be taken up at scale; their involvement should be part of the assessment criteria of any research proposal. The new global architecture, with the Sustainable Development Goals and the Global Strategy for Women’s, Children’s and Adolescents’ Health, ensures that MNH remains high on the political agenda. However, we must move from political commitment to action, via the creation and dissemination of evidence. The commitment of the research community should go beyond conducting and publishing research findings: from conception until the use of results, any research should be carried out in continuous partnership— with policy makers, politicians, development partners, and the media— to ensure that evidence is properly translated into policy and practice. We are far from reaching the goal of safe pregnancy and childbirth for all women and girls, in all countries. Research and innovation are essential ingredients for progress. The European Union has invested over €690 million in research directly related to MNH in 2007–13, and will continue its commitment under Horizon 2020, with new funding modalities like the Birth Day Prize, which aim to mobilise new and innovative actors.

Chronic respiratory diseases and lung cancer research: a perspective from the European Union

Chronic respiratory diseases (CRDs) are chronic diseases of the airways and other structures of the lungs. Major CRDs are asthma and respiratory allergies, chronic obstructive pulmonary disease (COPD), occupational lung diseases, sleep apnoea syndrome and pulmonary hypertension. Globally, they affect 1 billion people and account for 7% of all deaths worldwide (4.2 million deaths) [1]. Lung cancer adds to this number another 1.4 million deaths annually (2.4%) [2]. Of the communicable lung diseases, tuberculosis is by far the most important. In 2012, 1.3 million people were killed by tuberculosis and 8.6 million new cases required treatment [3]. The European Union fosters cutting-edge research and innovation in chronic respiratory diseases and lung cancer http://ow.ly/RKnu7

Emphasising the European Union's Commitment to Cancer Research: A Helicopter View of the Seventh Framework Programme for Research and Technological Development

This article discusses the efforts undertaken in the European Union toward basic, translational, and clinical cancer research on prevention, early diagnosis, prognosis, treatment, cancer control, quality of life, and survivorship.

European strategy for vaccine development against infectious diseases

Immunisation efforts save millions of lives every year, but vaccines hold the potential to deliver even greater health benefits for mankind. Vaccine research and development is highly complex, and it requires concerted public funding efforts to support. In this paper we discuss EU funding priorities and the resulting recent advancements in European vaccine research, and we lay out the EU strategy for aiding promising vaccine candidates to successfully reach the market.

Better Safe Than Sorry: Ethics Review in European Union-Funded Health Research

Public scrutiny and the increasing number of projects addressing later stages of the research and innovation process announced the need for an enhanced attention to be paid to identify and address ethics concerns. Ex-ante ethics review as implemented in EU-funded health research and a proactive ethics management are a genuinely useful exercise and ensures top-quality research, from the lab to the patient.