Reproducibility, relevance and reliability as barriers to efficient and credible biomedical technology translation.

Biomedical research accuracy and relevance for improving healthcare are increasingly identified as costly problems. Basic research data quality, reporting and methodology, and reproducibility are common factors implicated in this challenge. Preclinical models of disease and therapy, largely conducted in rodents, have known deficiencies in replicating most human conditions. Their translation to human results is acknowledged to be poor for decades. Clinical data quality and quantity is also recognized as deficient; gold standard randomized clinical trials are expensive. Few solid conclusions from clinical studies are replicable and many remain unpublished. The translational pathway from fundamental biomedical research through to innovative solutions handed to clinical practitioners is therefore highly inefficient and costly in terms of wasted resources, early claims from fundamental discoveries never witnessed in humans, and few new, improved solutions available clinically for myriad diseases. Improving this biomedical research strategy and resourcing for reliability, translational relevance, reproducibility and clinical impact requires careful analysis and consistent enforcement at both funding and peer review levels.

RadioTransNet: Preclinical research network coordinated at the SFRO and SFPM.

The RadioTransNet programme launched under the auspices of French societies for radiation oncology (SFRO) and medical physics (SFPM) was approved by the French national cancer institute (INCa) in December 2018 and is dedicated to proposing a relevant national and transversal structure for preclinical research including translational research in radiation oncology with well-defined priority areas of research. Its activities, coordinated by a scientific committee that includes radiation oncologists, medical physicists, academic biologists, are structured around several main areas, i.e.: target volume definition, interaction of radiation with normal tissues, combined treatments and modern dose calculation approaches. Four work packages have been created in these areas and are associated with other objectives pertaining to fundamental radiobiology, early implementation of new drugs in a preclinical setting, contribution of imaging in this task, research in medical physics including transversal components such as medical oncology, radiology, nuclear medicine and also cost/efficiency evaluation. All these tasks will be included in a national network that uses the complementary expertise provided by partners involved in the scheme. Calls for proposals will be selected by the scientific council to be submitted to INCa and the various academic associations to obtain funding for the human and technical resources required to conduct under optimal conditions projects in preclinical and translational research in radiation-oncology.

Teaming for excellence: challenges and collaboration in the world of reproductive clinical and translational research.

To succeed in the conduct of clinical trials in reproductive medicine, teams must be trained and cultivated to collaborate and achieve a common goal. Here I share my personal experiences and lessons learned in teaming in the research setting by covering topics in time management, resource allocation, collaboration, publishing, and communication.

European Biomedical Research Infrastructures and the Fight against COVID-19 Pandemic.

The study aims to assess the role of EU biomedical research infrastructures in the fight against the COVID-19 pandemic and to analyze their response to the challenges associated with the spread of the new pathogen. Materials and Methods: We analyzed the materials of the Seventh Framework Program for Research and Technological Development (FP7, 2007-2013) of the EU and the Eighth Framework Program "Horizon 2020" (FP8, 2014-2020), official reports of the European Strategic Forum on Research Infrastructures, expert reports, as well as documents of the European Commission, the COVID-19 Data Portal, and other relevant sources of information. Results: The analysis revealed that the mechanisms created within the united European research community provided for a flexible response to the emerging threat of COVID-19 as soon as January-May 2020. In particular, information channels were established to timely analyze the research results and coordinate the efforts in the fight against COVID-19. The biomedical infrastructures created in the EU and proved successful earlier have now been mobilized to search for ways of preventing and treating COVID-19. These mechanisms facilitated communication and data exchange between various research institutions and thus laid the ground for new achievements in this area. Conclusion: The decisions taken to combat the COVID-19 pandemic have convincingly illustrated that the EU research infrastructures, integrated into a united ecosystem, are highly adaptable and flexible, which allows to realign priorities in a short time and to create instruments that enable scientists to respond to new challenges.

Interrogating the World Bank's role in global health knowledge production, governance, and finance.

BACKGROUND: In the nearly half century since it began lending for population projects, the World Bank has become one of the largest financiers of global health projects and programs, a powerful voice in shaping health agendas in global governance spaces, and a mass producer of evidentiary knowledge for its preferred global health interventions. How can social scientists interrogate the role of the World Bank in shaping 'global health' in the current era? MAIN BODY: As a group of historians, social scientists, and public health officials with experience studying the effects of the institution's investment in health, we identify three challenges to this research. First, a future research agenda requires recognizing that the Bank is not a monolith, but rather has distinct inter-organizational groups that have shaped investment and discourse in complicated, and sometimes contradictory, ways. Second, we must consider how its influence on health policy and investment has changed significantly over time. Third, we must analyze its modes of engagement with other institutions within the global health landscape, and with the private sector. The unique relationships between Bank entities and countries that shape health policy, and the Bank's position as a center of research, permit it to have a formative influence on health economics as applied to international development. Addressing these challenges, we propose a future research agenda for the Bank's influence on global health through three overlapping objects of and domains for study: knowledge-based (shaping health policy knowledge), governance-based (shaping health governance), and finance-based (shaping health financing). We provide a review of case studies in each of these categories to inform this research agenda. CONCLUSIONS: As the COVID-19 pandemic continues to rage, and as state and non-state actors work to build more inclusive and robust health systems around the world, it is more important than ever to consider how to best document and analyze the impacts of Bank's financial and technical investments in the Global South.

Pilares para la excelencia en las unidades de nutrición: la investigación / Pillars for excellence in nutrition units - Research

Investigar en nutrición clínica y dietética consiste en "realizar actividades intelectuales y experimentales de modo sistemático con el propósito de aumentar los conocimientos de esta materia". La investigación biomédica que se realiza en las unidades de nutrición clínica y dietética (UNCyD) debe ser clínico-traslacional, entendida como la forma más rápida de conseguir que los nuevos conocimientos científicos se transfieran no solamente a la investigación clínica sino también a la práctica asistencial. Cuando las UNCyD realizan investigación, independientemente del tipo y la extensión, alcanzan mayores cotas de calidad en la atención sanitaria que prestan a sus usuarios. La práctica clínica y la investigación científica son actividades que constituyen una acción continuada e indisoluble. Por ello, tanto los responsables de las gerencias sanitarias como los de las unidades de nutrición y todos sus miembros tienen la obligación de fomentar la investigación. En el artículo se realiza un breve repaso histórico del nacimiento de la nutrición clínica como disciplina científica, se nombra someramente la legislación que sustenta la investigación biomédica, se proponen las principales claves para potenciar la investigación en las UNCyD y, por último, se orienta sobre las principales vías de financiación y sobre cómo realizar la transferencia y difusión de los resultados

Research in clinical nutrition and dietetics consists of "carrying out intellectual and experimental activities in a systematic way with the purpose of increasing knowledge on this topic." The biomedical research carried out in clinical nutrition and dietetics units (UNCyDs) must be clinical-translational, which is understood as the fastest way to ensure that new scientific knowledge is transferred not only to clinical research but also to clinical practice. When UNCyDs conduct research, regardless of type and extent, they achieve higher quality standards in the health care they provide to their users. Clinical practice and scientific research are activities that constitute a continuous, indissoluble action. For this reason, both those responsible for health management and nutrition units and all their members have an obligation to promote research. In this article, a brief historical review of the birth of clinical nutrition as a scientific discipline is made, the legislation that supports biomedical research is briefly mentioned, the main keys to promote research in UNCyD are proposed, and finally orientation is offered on the main funding for biomedical research programs, and how to transfer and disseminate results

Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.

Asia-inclusive global development of pevonedistat: Clinical pharmacology and translational research enabling a phase 3 multiregional clinical trial.

The investigational NEDD8-activating enzyme inhibitor pevonedistat is being evaluated in combination with azacitidine versus single-agent azacitidine in patients with higher-risk myelodysplastic syndrome (higher-risk MDS), higher-risk chronic myelomonocytic leukemia (higher-risk CMML), or low-blast acute myeloid leukemia (AML) in a Phase 3 trial PANTHER. To support Asia-inclusive global development, we applied multiregional clinical trial (MRCT) principles of the International Conference on Harmonisation E17 guidelines by evaluating similarity in drug-related and disease-related intrinsic and extrinsic factors. A PubMed literature review (January 2000-November 2019) supported similarity in epidemiology of higher-risk MDS, AML, and CMML in Western and East Asian populations. Furthermore, the treatment of MDS/AML was similar in both East Asian and Western regions, with the same dose of azacitidine being the standard of care. Median overall survival in MDS following azacitidine treatment was generally comparable across regions, and the types and frequencies of molecular alterations in AML and MDS were comparable. Dose-escalation studies established the same maximum tolerated dose of pevonedistat in combination with azacitidine in Western and East Asian populations. Pevonedistat clearance was similar across races. Taken together, conservation of drug-related and disease-related intrinsic and extrinsic factors supported design of an Asia-inclusive Phase 3 trial and a pooled East Asian region. A sample size of ~ 30 East Asian patients (of ~ 450 randomized) was estimated as needed to demonstrate consistency in efficacy relative to the global population. This analysis is presented as an exemplar to illustrate application of clinical pharmacology and translational science principles in designing Asia-inclusive MRCTs. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Azacitidine is the standard of care for myelodysplastic syndromes/low-blast acute myeloid leukemia (AML) across Western and East Asian patients. The first-in-class small-molecule inhibitor of NEDD8-activating enzyme, pevonedistat, has been investigated as a single agent in multiple studies of hematologic and nonhematologic malignancies and in combination with azacitidine in elderly patients with untreated AML. WHAT QUESTION DID THIS STUDY ADDRESS? By applying clinical pharmacology and translational science and International Conference on Harmonisation E17 principles, this study designed an East Asian-inclusive global pivotal Phase 3 trial of pevonedistat, taking into consideration drug-related and disease-related intrinsic and extrinsic factors. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? These analyses provide scientific rationale for Asia-inclusive globalization of the pivotal, Phase 3 PANTHER trial and for pooling clinical data across the East Asian region for assessing consistency in efficacy. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? We developed a framework to facilitate efficient global clinical development of investigational therapies for rare cancers and orphan diseases in Asia-inclusive multiregional clinical trials.

Teamwork at the Bench: Strategies for Collaborative Surgical Science in a Pandemic.

The Center for Basic and Translational Science was formed to address the unique challenges faced by surgeon-scientists. Shortly after its inception, COVID-19 upended research workflows at our institution. We discuss how the collaborative Center for Basic and Translational Science framework was adapted to support laboratories during the pandemic by assisting with ramp-down, promoting mentorship and community building, and maintaining research productivity.

Road to effective data curation for translational research.

Translational research today is data-intensive and requires multi-stakeholder collaborations to generate and pool data together for integrated analysis. This leads to the challenge of harmonization of data from different sources with different formats and standards, which is often overlooked during project planning and thus becomes a bottleneck of the research progress. We report on our experience and lessons learnt about data curation for translational research garnered over the course of the European Translational Research Infrastructure & Knowledge management Services (eTRIKS) program (https://www.etriks.org), a unique, 5-year, cross-organizational, cross-cultural collaboration project funded by the Innovative Medicines Initiative of the EU. Here, we discuss the obstacles and suggest what steps are needed for effective data curation in translational research, especially for projects involving multiple organizations from academia and industry.

The future of translational research on alcohol use disorder.

In March 2019, a scientific meeting was held at the University of California, Los Angeles (UCLA) Luskin Center to discuss approaches to expedite the translation of neurobiological insights to advances in the treatment of alcohol use disorder (AUD). A guiding theme that emerged was that while translational research in AUD is clearly a challenge, it is also a field ripe with opportunities. Herein, we seek to summarize and disseminate the recommendations for the future of translational AUD research using four sections. First, we briefly review the current landscape of AUD treatment including the available evidence-based treatments and their uptake in clinical settings. Second, we discuss AUD treatment development efforts from a translational science viewpoint. We review current hurdles to treatment development as well as opportunities for mechanism-informed treatment. Third, we consider models of translational science and public health impact. Together, these critical insights serve as the bases for a series of recommendations and future directions. Towards the goal of improving clinical care and population health for AUD, scientists are tasked with bolstering the clinical applicability of their research findings so as to expedite the translation of knowledge into patient care.