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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.

Integrates the various disciplines of the science of health disparities in one comprehensive volume The Science of Health Disparities Research is an indispensable source of up-to-date information on clinical and translational health disparities science. Building upon the advances in health disparities research over the past decade, this authoritative volume informs policies and practices addressing the diseases, disorders, and gaps in health outcomes that are more prevalent in minority populations and socially disadvantaged communities. Contributions by recognized scholars and leaders in the field—featuring contemporary research, conceptual models, and a broad range of scientific perspectives—provide an interdisciplinary approach to reducing inequalities in population health, encouraging community engagement in the research process, and promoting social justice. In-depth chapters help readers better understand the specifics of minority health and health disparities while demonstrating the importance of advancing theory, refining measurement, improving investigative methods, and diversifying scientific research. In 26 chapters, the book examines topics including the etiology of health disparities research, the determinants of population health, research ethics, and research in African American, Asians, Latino, American Indian, and other vulnerable populations. Providing a unified framework on the principles and applications of the science of health disparities research, this important volume: * Defines the field of health disparities science and suggests new directions in scholarship and research * Explains basic definitions, principles, and concepts for identifying, understanding and addressing health disparities * Provides guidance on both conducting health disparities research and translating the results * Examines how social, historical and contemporary injustices may influence the health of racial and ethnic minorities * Illustrates the increasing national and global importance of addressing health disparities * Discusses population health training, capacity-building, and the transdisciplinary tools needed to advance health equity A significant contribution to the field, The Science of Health Disparities Research is an essential resource for students and basic and clinical researchers in genetics, population genetics, and public health, health care policymakers, and epidemiologists, medical students, and clinicians, particularly those working with minority, vulnerable, or underserved populations.

In the era of precision medicine, digital technologies and artificial intelligence, drug discovery and development face unprecedented opportunities for product and business model innovation, fundamentally changing the traditional approach of how drugs are discovered, developed and marketed. Critical to this transformation is the adoption of new technologies in the drug development process, catalyzing the transition from serendipity-driven to data-driven medicine. This paradigm shift comes with a need for both translation and precision, leading to a modern Translational Precision Medicine approach to drug discovery and development. Key components of Translational Precision Medicine are multi-omics profiling, digital biomarkers, model-based data integration, artificial intelligence , biomarker-guided trial designs and patient-centric companion diagnostics. In this review, we summarize and critically discuss the potential and challenges of Translational Precision Medicine from a cross-industry perspective.

Comparative oncology clinical trials play an important and growing role in cancer research and drug development efforts. These trials, typically conducted in companion (pet) dogs, allow assessment of novel anticancer agents and combination therapies in a veterinary clinical setting that supports serial biologic sample collections and exploration of dose, schedule and corresponding pharmacokinetic/pharmacodynamic relationships. Further, an intact immune system and natural co-evolution of tumour and microenvironment support exploration of novel immunotherapeutic strategies. Substantial improvements in our collective understanding of the molecular landscape of canine cancers have occurred in the past 10 years, facilitating translational research and supporting the inclusion of comparative studies in drug development. The value of the approach is demonstrated in various clinical trial settings, including single-agent or combination response rates, inhibition of metastatic progression and randomized comparison of multiple agents in a head-to-head fashion. Such comparative oncology studies have been purposefully included in the developmental plan for several US FDA-approved and up-and-coming anticancer drugs. Challenges for this field include keeping pace with technology and data dissemination/harmonization, improving annotation of the canine genome and immune system, and generation of canine-specific validated reagents to support integration of correlative biology within clinical trial efforts.This Review discusses the role of comparative oncology studies between pet dogs and humans with an emphasis on selected canine tumour types that represent those with the most translational benefit to humans and those possessing important molecular intersections with human malignancies.

Starting with the launch of the Human Genome Project three decades ago, and continuing after its completion in 2003, genomics has progressively come to have a central and catalytic role in basic and translational research. In addition, studies increasingly demonstrate how genomic information can be effectively used in clinical care. In the future, the anticipated advances in technology development, biological insights, and clinical applications (among others) will lead to more widespread integration of genomics into almost all areas of biomedical research, the adoption of genomics into mainstream medical and public-health practices, and an increasing relevance of genomics for everyday life. On behalf of the research community, the National Human Genome Research Institute recently completed a multi-year process of strategic engagement to identify future research priorities and opportunities in human genomics, with an emphasis on health applications. Here we describe the highest-priority elements envisioned for the cutting-edge of human genomics going forward—that is, at ‘The Forefront of Genomics’. In this Perspective, authors from the National Human Genome Research Institute (NHGRI) present a vision for human genomics research for the coming decade.

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.