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Background The need for high-quality evidence that is applicable in real-world, routine settings continues to increase. Pragmatic trials are designed to evaluate the effectiveness of interventions in real-world settings, whereas explanatory trials aim to test whether an intervention works under optimal situations. There is a continuum between explanatory and pragmatic trials. Most trials have aspects of both, making it challenging to label and categorize a trial and to evaluate its potential for translation into practice. Methods We summarize our experience applying the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) combined with external validity items based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to three studies to provide a more robust and comprehensive assessment of trial characteristics related to translation of research. We summarize lessons learned using domains from the combined frameworks for use in study planning, evaluating specific studies, and reviewing the literature and make recommendations for future use. Results A variety of coders can be trained to use the PRECIS and RE-AIM domains. These domains can also be used for diverse purposes, content areas, and study types, but are not without challenges. Both PRECIS and RE-AIM domains required modification in two of the three studies to evaluate and rate domains specific to study type. Lessons learned involved: dedicating enough time for training activities related to the domains; use of reviewers with a range of familiarity with specific study protocols; how to best adapt ratings that reflect complex study designs; and differences of opinion regarding the value of creating a composite score for these criteria. Conclusions Combining both frameworks can specifically help identify where and how a study is and is not pragmatic. Using both PRECIS and RE-AIM allows for standard reporting of key study characteristics related to pragmatism and translation. Such measures should be used more consistently to help plan more pragmatic studies, evaluate progress, increase transparency of reporting, and integrate literature to facilitate translation of research into practice and policy.

Despite regenerative medicine (RM) being one of the hottest topics in biotechnology for the past 3 decades, it is generally acknowledged that the field’s performance at the bedside has been somewhat disappointing. This may be linked to the novelty of these technologies and their disruptive nature, which has brought an increasing level of complexity to translation. Therefore, we look at how the historical development of the RM field has changed the translational strategy. Specifically, we explore how the pursuit of such novel regenerative therapies has changed the way experts aim to translate their ideas into clinical applications, and then identify areas that need to be corrected or reinforced in order for these therapies to eventually be incorporated into the standard‐of‐care. This is then linked to a discussion of the preclinical and postclinical challenges remaining today, which offer insights that can contribute to the future progression of RM.

Translation of genomic discoveries into patient care is slowly becoming a reality in developed economies around the world. In contrast, low- and middle-income countries (LMIC) have participated minimally in genomic research for several reasons including the lack of coherent national policies, the limited number of well-trained genomic scientists, poor research infrastructure, and local economic and cultural challenges. Recent initiatives such as the Human Heredity and Health in Africa (H3Africa), the Qatar Genome Project, and the Mexico National Institute of Genomic Medicine (INMEGEN) that aim to address these problems through capacity building and empowerment of local researchers have sparked a paradigm shift. In this short communication, we describe experiences of small-scale medical genetics and translational genomic research programs in LMIC. The lessons drawn from these programs drive home the importance of addressing resource, policy, and sociocultural dynamics to realize the promise of precision medicine driven by genomic science globally. By echoing lessons from a bench-to-community translational genomic research, we advocate that large-scale genomic research projects can be successfully linked with health care programs. To harness the benefits of genomics-led health care, LMIC governments should begin to develop national genomics policies that will address human and technology capacity development within the context of their national economic and sociocultural uniqueness. These policies should encourage international collaboration and promote the link between the public health program and genomics researchers. Finally, we highlight the potential catalytic roles of the global community to foster translational genomics in LMIC.

Keywords: Videolaryngoscopy, Simulation, Novice, Physician-trainee, Intubation skill

Key Points This Review describes recent progress in directing human pluripotent stem cells (hPSCs) into specific progeny that could have therapeutic purposes for a range of diseases. It also addresses major hurdles in the transition of hPSC-based cell therapies from the bench to the bedside. Neural induction of hPSCs can be achieved in several ways. Recent protocols use defined neural inducers — such as inhibitors of transforming growth factor-β (TGFβ) and bone morphogenetic protein (BMP) (that is, dual SMAD inhibition) — to greatly enhance the efficiency and the speed of neural induction. The derivation of dopamine neurons from hPSCs has been achieved a decade ago, but the cells did not show good engraftment. Recent data shows that those neurons lacked expression of forkhead box protein A2 (FOXA2), which is a DNA-binding transcription factor that is fundamental for authentic midbrain identity. A novel protocol derives dopamine neurons through a floor plate intermediate, which show genetic, biochemical and physiological features of authentic midbrain neurons. They also survive and ameliorate Parkinson's disease-like behaviour in vivo . Improved protocols for the derivation of medium spiny striatal neurons from hPSCs has been reported, and evidence shows survival and behavioural improvement in a lesion model of Huntington's disease. The derivation of glial cells from hPSCs is faced with the challenge of protracted developmental timing in vitro , which is similar to the in vivo situation. The derivation of oligodendrocytes has been achieved using long-term in vitro cultures; these cells have been grafted in neonatal Shiverer -expressing mice with good cell survival, remyelination and extended lifespan in these mice. The current derivation of non-neural cell types — such as cardiomyocytes, pancreatic islet cells and engraftable haematopoietic stem cells — faces substantial challenges owing to the immature nature of the differentiated cells (for cardiomyocytes), the need for in vivo differentiation (for pancreatic islet cells) and poor in vivo homing (for haematopoietic stem cells). New developments in cell differentiation include the use of potent small molecules that allow the direct manipulation of multiple signalling pathways and, in some cases, the acceleration of differentiation timelines. Other approaches include cell purification and three-dimensional cultures that harness the self-organizing potential of hPSC-derived lineages. Defining cell identity in vitro is a fundamental element in designing directed differentiation strategies and includes expression of cell type-specific markers, transcriptional profiles and assessments of the epigenetic or enhancer landscapes. Assessment of in vivo function includes electrophysiology, the use of genetically encoded calcium sensors, microdialysis and optogenetic techniques, as well as behavioural studies. Autologous cell sources, such as patient-derived induced pluripotent stem cells, are of great interest but currently face substantial hurdles for clinical implementation that are related to safety and regulatory requirements. The translation of direct reprogramming and nuclear transfer strategies are in early stages of development. A spinal cord trial using human embryonic stem cell (hESC)-derived oligodendrocytes has not reported any major adverse effects, although the trial has been abandoned. Ongoing clinical trials using hESC-derived retinal pigment epithelial in eye repair are promising. The derivation of disease-relevant cell types from pluripotent stem cells holds much promise for disease therapy. The recent progress in directed differentiation and the challenges ahead are discussed in this Review. After years of incremental progress, several recent studies have succeeded in deriving disease-relevant cell types from human pluripotent stem cell (hPSC) sources. The prospect of an unlimited cell source, combined with promising preclinical data, indicates that hPSC technology may be on the verge of clinical translation. In this Review, we discuss recent progress in directed differentiation, some of the new technologies that have facilitated the success of hPSC therapies and the remaining hurdles on the road towards developing hPSC-based cell therapies.

Society makes substantial investments in biomedical research, searching for ways to better human health. The product of this research is principally information published in scientific journals. Continued investment in science relies on society’s confidence in the accuracy, honesty, and utility of research results. A recent focus on productivity has dominated the competitive evaluation of scientists, creating incentives to maximize publication numbers, citation counts, and publications in high-impact journals. Some studies have also suggested a decreasing quality in the published literature. The efficiency of society’s investments in biomedical research, in terms of improved health outcomes, has not been studied. We show that biomedical research outcomes over the last five decades, as estimated by both life expectancy and New Molecular Entities approved by the Food and Drug Administration, have remained relatively constant despite rising resource inputs and scientific knowledge. Research investments by the National Institutes of Health over this time correlate with publication and author numbers but not with the numerical development of novel therapeutics. We consider several possibilities for the growing input-outcome disparity including the prior elimination of easier research questions, increasing specialization, overreliance on reductionism, a disproportionate emphasis on scientific outputs, and other negative pressures on the scientific enterprise. Monitoring the efficiency of research investments in producing positive societal outcomes may be a useful mechanism for weighing the efficacy of reforms to the scientific enterprise. Understanding the causes of the increasing input-outcome disparity in biomedical research may improve society’s confidence in science and provide support for growing future research investments.

Introduction The use of social media is rapidly changing how educational content is delivered and knowledge is translated for physicians and trainees. This scoping review aims to aggregate and report trends on how health professions educators harness the power of social media to engage physicians for the purposes of knowledge translation and education. Methods A scoping review was conducted by searching four databases (PubMed, Scopus, Embase, and ERIC) for publications emerging between 1990 to March 2018. Articles about social media usage for teaching physicians or their trainees for the purposes of knowledge translation or education were included. Relevant themes and trends were extracted and mapped for visualization and reporting, primarily using the Cook, Bordage, and Schmidt framework for types of educational studies (Description, Justification, and Clarification). Results There has been a steady increase in knowledge translation and education-related social media literature amongst physicians and their trainees since 1996. Prominent platforms include Twitter ( n  = 157), blogs ( n  = 104), Facebook ( n  = 103), and podcasts ( n  = 72). Dominant types of scholarship tended to be descriptive studies and innovation reports. Themes related to practice improvement, descriptions of the types of technology, and evidence-based practice were prominently featured. Conclusions Social media is ubiquitously used for knowledge translation and education targeting physicians and physician trainees. Some best practices have emerged despite the transient nature of various social media platforms. Researchers and educators may engage with physicians and their trainees using these platforms to increase uptake of new knowledge and affect change in the clinical environment.

Interindividual variability in drug efficacy and toxicity is a major challenge in clinical practice. Variations in drug pharmacokinetics (PKs) and pharmacodynamics (PDs) can be, in part, explained by polymorphic variants in genes encoding drug metabolizing enzymes and transporters (absorption, distribution, metabolism, and excretion) or in genes encoding drug receptors. Pharmacogenomics (PGx) has allowed the identification of predictive biomarkers of drug PKs and PDs and the current knowledge of genome‐disease and genome‐drug interactions offers the opportunity to optimize tailored drug therapy. High‐throughput PGx genotyping, from targeted to more comprehensive strategies, allows the identification of PK/PD genotypes to be developed as clinical predictive biomarkers. However, a biomarker needs a robust process of validation followed by clinical‐grade assay development and must comply to stringent regulatory guidelines. We here discuss the methodological challenges and the emerging technological tools in PGx biomarker discovery and validation, at the crossroad among molecular genetics, bioinformatics, and clinical medicine.

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. This study reveals the attributes of cancer centres based on data from 40 large European cancer centres, showing that Comprehensive Cancer Centres have significantly greater output of peer‐reviewed publications and clinical trials than other centres, and that the quality of multidisciplinarity is well established in all accredited cancer centres.