Implementing genomic medicine in the clinic: The future is here

National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Genetics in medicine: official journal of the American College of Medical Genetics (Impact Factor: 7.33). 01/2013; 15(4). DOI: 10.1038/gim.2012.157
Source: PubMed

ABSTRACT Although the potential for genomics to contribute to clinical care has long been anticipated, the pace of defining the risks and benefits of incorporating genomic findings into medical practice has been relatively slow. Several institutions have recently begun genomic medicine programs, encountering many of the same obstacles and developing the same solutions, often independently. Recognizing that successful early experiences can inform subsequent efforts, the National Human Genome Research Institute brought together a number of these groups to describe their ongoing projects and challenges, identify common infrastructure and research needs, and outline an implementation framework for investigating and introducing similar programs elsewhere. Chief among the challenges were limited evidence and consensus on which genomic variants were medically relevant; lack of reimbursement for genomically driven interventions; and burden to patients and clinicians of assaying, reporting, intervening, and following up genomic findings. Key infrastructure needs included an openly accessible knowledge base capturing sequence variants and their phenotypic associations and a framework for defining and cataloging clinically actionable variants. Multiple institutions are actively engaged in using genomic information in clinical care. Much of this work is being done in isolation and would benefit from more structured collaboration and sharing of best practices.
Genet Med 2013:15(4):258–267

Download full-text


Available from: Marc S Williams, Mar 04, 2014
35 Reads
  • Source
    • "Although currently not in widespread use, clinical genomic sequencing can guide cancer therapy selection and monitoring [Garraway, 2013; McLeod, 2013; Van Allen et al., 2014] and is being applied in many other clinical situations [Bowdin et al., 2014; Dewey et al., 2014]. Despite predicted clinical utility, experts have identified factors that preclude its rapid clinical adoption, and limitations that should be addressed in the informed consent process [Burke et al., 2013; Evans and Khoury, 2013; Manolio et al., 2013; McLeod, 2013; Biesecker and Green, 2014; Dewey et al., 2014; Vrijenhoek et al., 2015]. To briefly summarize, technical limitations prevent the identification of all disease-associated variants, and the reliance on incomplete and error-prone variant databases prevents the unambiguous classification of many variants that are identified. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite the increased utilization of genome and exome sequencing, little is known about the actual content and process of informed consent for sequencing. We addressed this by interviewing 29 genetic counselors and research coordinators experienced in obtaining informed consent for sequencing in research and clinical settings. Interviews focused on the process and content of informed consent; patients/participants' common questions, concerns and misperceptions; and challenges to obtaining informed consent. Content analysis of transcribed interviews revealed that the main challenges to obtaining consent related to the broad scope and uncertainty of results, and patient/participants' unrealistic expectations about the likely number and utility of results. Interviewees modified their approach to sessions according to contextual issues surrounding the indication for testing, type of patient, and timing of testing. With experience, most interviewees structured sessions to place less emphasis on standard elements in the consent form and technological aspects of sequencing. They instead focused on addressing misperceptions and helping patients/participants develop realistic expectations about the types and implications of possible results, including secondary findings. These findings suggest that informed consent sessions should focus on key issues that may be misunderstood by patients/participants. Future research should address the extent to which various stakeholders agree on key elements of informed consent. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 07/2015; DOI:10.1002/ajmg.a.37256 · 2.16 Impact Factor
  • Source
    • "Things like family health history, symptoms, medications, pathology reports, and patient outcomes can be as important to an accurate diagnosis and treatment as the underlying genetic makeup [5]. As the power of a wider breadth of data is realized, the network that results from numerous institutions sharing data across a range of diseases will have large statistics to drive insight [6]. The data challenge will be different but no less complex. "
    Genomics Data 12/2014; 2:49. DOI:10.1016/j.gdata.2014.04.001
  • Source
    • "Drawing from discussions in other disciplines, several recommendations can be made for near-term efforts to promote translation research in addiction therapeutics. A general goal is to evaluate candidate pharmacogenetic applications with approaches that balance methodological rigor with clinical applicability [8,13,54]. To meet this aim, a comprehensive, portfolio-based approach to translation research has been recommended [8,12]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite advances in characterizing genetic influences on addiction liability and treatment response, clinical applications of these efforts have been slow to evolve. Although challenges to clinical translation remain, stakeholders already face decisions about evidentiary thresholds for the uptake of pharmacogenetic tests in practice. There is optimism about potential pharmacogenetic applications for the treatment of alcohol use disorders, with particular interest in the OPRM1 A118G polymorphism as a moderator of naltrexone response. Findings from human and animal studies suggest preliminary evidence for the clinical validity of this association; on this basis, arguments for clinical implementation can be made in accordance with existing frameworks for the uptake of genomic applications. However, generating evidence-based guidelines requires evaluating the clinical utility of pharmacogenetic tests. This goal will remain challenging, largely due to minimal data to inform clinical utility estimates. The pace of genomic discovery highlights the need for clinical utility and implementation research to inform future translation efforts. Near-term implementation of promising pharmacogenetic tests can help expedite this goal, generating an evidence base to enable efficient translation as additional gene-drug associations are discovered.
    Addiction science & clinical practice 09/2014; 9(1):20. DOI:10.1186/1940-0640-9-20
Show more