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Strategic vision for improving human health at The Forefront of Genomics
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.
Journal Article
Interpreting biomedical science : experiment, evidence, and belief
Interpreting Biomedical Science: Experiment, Evidence, and Belief discusses what can go wrong in biological science, providing an unbiased view and cohesive understanding of scientific methods, statistics, data interpretation, and scientific ethics that are illustrated with practical examples and real-life applications. Casting a wide net, the reader is exposed to scientific problems and solutions through informed perspectives from history, philosophy, sociology, and the social psychology of science. The book shows the differences and similarities between disciplines and different eras and illustrates the concept that while sound methodology is necessary for the progress of science, we cannot succeed without a right culture of doing things.
Book
Diversity in Clinical and Biomedical Research: A Promise Yet to Be Fulfilled
Esteban Gonzalez Burchard and colleagues explore how making medical research more diverse would aid not only social justice but scientific quality and clinical effectiveness, too.Esteban Gonzalez Burchard and colleagues explore how making medical research more diverse would aid not only social justice but scientific quality and clinical effectiveness, too.
Journal Article
Unreliable : bias, fraud, and the reproducibility crisis in biomedical research
\"Scientists specializing in the in-depth analysis of the published scientific literature have to the conclusion that a large part of the scientific literature covers results that cannot be replicated in other independent laboratories. Scientists take this to mean that the results are unreliable or untrue. In this book, biomedical researcher Csaba Szabo summarizes the causes and consequences of this so-called \"reproducibility crisis\" in biomedical research. The range of causes is wide, from the specificities of the methods used, through various pitfalls in the design of experiments and analysis of experimental data (e.g., confirmation bias), plagiarism and deliberate data falsification, to the systematic publication of fictitious experiments that have never been performed. Through a few blatant examples - e.g. Anil Potti (Duke University); Piero Anversa (Harvard University) - Szabo describes the damaging impact that blatant fraud can have on the development of an entire field of science, and introduces some of the maverick \"science investigators\" - often working in anonymity - who devote their lives to tracking down and exposing scientific fraudsters. The book also answers the questions (a) what individual and systemic factors are involved in allowing these phenomena to occur, (b) why the appropriate steps have not been taken to control them, and (c) what the implications of the crisis are for the future of medicine and, within it, for the development of new drugs\"-- Provided by publisher.
BOOK
A reinvestigation of recruitment to randomised, controlled, multicenter trials: a review of trials funded by two UK funding agencies
Background
Randomised controlled trials (RCTs) are the gold standard assessment for health technologies. A key aspect of the design of any clinical trial is the target sample size. However, many publicly-funded trials fail to reach their target sample size. This study seeks to assess the current state of recruitment success and grant extensions in trials funded by the Health Technology Assessment (HTA) program and the UK Medical Research Council (MRC).
Methods
Data were gathered from two sources: the National Institute for Health Research (NIHR) HTA Journal Archive and the MRC subset of the International Standard Randomised Controlled Trial Number (ISRCTN) register. A total of 440 trials recruiting between 2002 and 2008 were assessed for eligibility, of which 73 met the inclusion criteria. Where data were unavailable from the reports, members of the trial team were contacted to ensure completeness.
Results
Over half (55%) of trials recruited their originally specified target sample size, with over three-quarters (78%) recruiting 80% of their target. There was no evidence of this improving over the time of the assessment. Nearly half (45%) of trials received an extension of some kind. Those that did were no more likely to successfully recruit. Trials with 80% power were less likely to successfully recruit compared to studies with 90% power.
Conclusions
While recruitment appears to have improved since 1994 to 2002, publicly-funded trials in the UK still struggle to recruit to their target sample size, and both time and financial extensions are often requested. Strategies to cope with such problems should be more widely applied. It is recommended that where possible studies are planned with 90% power.
Journal Article
Reproducible, scalable, and shareable analysis pipelines with bioinformatics workflow managers
The rapid growth of high-throughput technologies has transformed biomedical research. With the increasing amount and complexity of data, scalability and reproducibility have become essential not just for experiments, but also for computational analysis. However, transforming data into information involves running a large number of tools, optimizing parameters, and integrating dynamically changing reference data. Workflow managers were developed in response to such challenges. They simplify pipeline development, optimize resource usage, handle software installation and versions, and run on different compute platforms, enabling workflow portability and sharing. In this Perspective, we highlight key features of workflow managers, compare commonly used approaches for bioinformatics workflows, and provide a guide for computational and noncomputational users. We outline community-curated pipeline initiatives that enable novice and experienced users to perform complex, best-practice analyses without having to manually assemble workflows. In sum, we illustrate how workflow managers contribute to making computational analysis in biomedical research shareable, scalable, and reproducible.This Perspective highlights workflow managers, which are useful for developing and managing complex bioinformatics pipelines.
Journal Article
Rescuing US biomedical research from its systemic flaws
The long-held but erroneous assumption of never-ending rapid growth in biomedical science has created an unsustainable hypercompetitive system that is discouraging even the most outstanding prospective students from entering our profession—and making it difficult for seasoned investigators to produce their best work. This is a recipe for long-term decline, and the problems cannot be solved with simplistic approaches. Instead, it is time to confront the dangers at hand and rethink some fundamental features of the US biomedical research ecosystem.
Journal Article