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?

Abstract

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.

Strengthening the reporting of genetic risk prediction studies: the GRIPS statement

“…Knowledge about genetic risk factors may be used to target diagnostic, preventive and therapeutic interventions for complex disorders based on a person's genetic risk or to complement existing risk models based on classical nongenetic factors such as the Framingham risk score for cardiovascular disease. Implementation of genetic risk prediction in health care requires a series of studies that encompass all phases of translational research [2,3], starting with a comprehensive evaluation of genetic risk prediction.…”

Modern Approaches to the Organization of Translational Research

“…4T concept. At the same time, Khoury et al include the studies on results of practical implementation of a new intervention into the translation, thus outlining stage T4 [19]. This stage may involve evaluation of medical technologies and pharmacoeconomic analysis.…”

Rethinking biobanking and translational medicine in the Netherlands: how the research process stands to matter for patient care

“…For instance, in the case of genomic medicine a four-phase translational model has been advanced in which the discovery of a candidate health application (that is, translational research phase one, or T1) is developed into a evidence-based guideline (T2) that is disseminated and taken up in health practice or Phase IV clinical trials (T3), which are then monitored at the population level for 'real world' health impact (T4). 15 Whereas models similar to this have been influential in steering research and care, they tend to focus their attention on how the products of research projects (that is, health applications, guidelines, and so on) are -or can be -fed into health-care practices. In this Viewpoint, a different perspective on the benefits of translational medicine and biobanking is forwarded.…”