Khoury MJ, Gwinn M, Yoon PW, et al.. The continuum of translation research in genomic medicine: how can we accelerate the appropriate integration of human genome discoveries into health care and disease prevention

National Office of Public Health Genomics Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
Genetics in medicine: official journal of the American College of Medical Genetics (Impact Factor: 7.33). 11/2007; 9(10):665-74. DOI: 10.1097/GIM.0b013e31815699d0
Source: PubMed


Advances in genomics have led to mounting expectations in regard to their impact on health care and disease prevention. In light of this fact, a comprehensive research agenda is needed to move human genome discoveries into health practice in a way that maximizes health benefits and minimizes harm to individuals and populations. We present a framework for the continuum of multidisciplinary translation research that builds on previous characterization efforts in genomics and other areas in health care and prevention. The continuum includes four phases of translation research that revolve around the development of evidence-based guidelines. Phase 1 translation (T1) research seeks to move a basic genome-based discovery into a candidate health application (e.g., genetic test/intervention). Phase 2 translation (T2) research assesses the value of a genomic application for health practice leading to the development of evidence-based guidelines. Phase 3 translation (T3) research attempts to move evidence-based guidelines into health practice, through delivery, dissemination, and diffusion research. Phase 4 translation (T4) research seeks to evaluate the "real world" health outcomes of a genomic application in practice. Because the development of evidence-based guidelines is a moving target, the types of translation research can overlap and provide feedback loops to allow integration of new knowledge. Although it is difficult to quantify how much of genomics research is T1, we estimate that no more than 3% of published research focuses on T2 and beyond. Indeed, evidence-based guidelines and T3 and T4 research currently are rare. With continued advances in genomic applications, however, the full continuum of translation research needs adequate support to realize the promise of genomics for human health.

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Available from: Muin J Khoury, Aug 29, 2014
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    • "It then continues with prioritizing, executing, and evaluating conservation actions, before the cycle is repeated and refined until goals are reached. Addressing the major steps in this cycle has also been recognized as key in other areas of applied genetics (Khoury et al. 2007). The 15 articles offered in this special issue cover not only a wide range of countries and species (from Cuba to "

    The Journal of heredity 08/2015; 106 Suppl 1(S1):423-7. DOI:10.1093/jhered/esv052 · 2.09 Impact Factor
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    • "A major barrier to the clinical translation of pharmacogenetics is the shortfall of data to inform estimates of clinical utility, contributing to the so-called “evidence dilemma” in genomic medicine [6,45]. This gap exists primarily at the T2 stage, such that even the most promising applications are rarely subjected to rigorous research to inform clinical utility profiles and implementation questions [6,12,46]. A consequence of this “T2 bottleneck” is that decisions about clinical implementation must be made absent comprehensive evidence for or against clinical utility—or else deferred indefinitely [6]. "
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    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
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    • "The clinical or public health applications of such variants are unclear, including whether knowledge of such genetic variants related to disease risk will lead to meaningful improvements in public health. The commercialization of genomic tests involving low-penetrance variants has outpaced our understanding of the communication, behavioral and social aspects of testing (Khoury et al., 2007; McBride et al., 2008). "
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    ABSTRACT: This study examines communication about limitations of genomic results interpretation for colon cancer risk during education and counseling of minority participants. As part of a larger study conducted from 2010 to 2012, participants recruited from a large primary care clinic were offered testing for a research panel of 3 genomic markers (single nucleotide polymorphisms or SNPs) for colorectal cancer risk. Genetic counselors conducted pre- and post-test sessions which included discussion of limitations of result interpretation due to the lack of racial/ethnic diversity in research populations from which risk data are derived. Sessions were audio-recorded, transcribed and thematically analyzed. Many participants did not respond directly to this limitation. Among the participants that responded directly to this race-related limitation, many responses were negative. However, a few participants connected the limited minority information about SNPs with the importance of their current research participation. Genetic counselor discussions of this limitation were bio-medically focused with limited explanations for the lacking data. The communication process themes identified included: low immediacy (infrequent use of language directly involving a participant), verbal dominance (greater speaking ratio of the counselor to the patient) and wide variation in the degree of interactivity (or the amount of turn-taking during the discussion). Placed within the larger literature on patient-provider communication, these present results provide insight into the dynamics surrounding race-related educational content for genomic testing and other emerging technologies. Clinicians may be better able to engage patients in the use of new genomic technology by increasing their awareness of specific communication processes and patterns during education or counseling sessions.
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