Translational Sequence


Translational Sequence





Figure 1: Overview of the phases of translation from T0 (Discovery Science) to T5 (Globalization). Note that in this model ‘translation’ is not depicted a linear series of events ranging from T0-T5; instead the model reflects the relationships between non-sequential phases of translation and demonstrates the possibility for multiple modes of ‘back-translation’.




Each stage delineates a two-step process with the results of one activity being translated to activities undertaken in the next stage along the pathway. 


Furthermore, back-translation is an iterative part of the process.  Every stage (and every "step") in a translational process or continuum incorporates bidirectional exchange with earlier stages, as needed, so that there are constant modifications and refinements.  If the results are negative or new, or unexpected findings occur, then the process refers back to prior translational phases. In a few uncommon cases, forward-translation may skip some steps (e.g., methods translation may get disseminated); however, such instances are uncommon.  


T0: The fundamental process of discovery, which is sometimes forgotten in the discussion of translational science. This phase also includes the translation of theory and findings from the basic sciences to applied theory, the latter with direct applicability to prevention. This phase corresponds to NIH Phase 1 of the five-phase model.


T1: Part of the now "classical" step of bench to bedside and involves the translation of applied theory and basic science findings to methods development (measures, analysis) and to program development. For example, T1 includes applied theories and prevention-relevant findings from animal and human basic science studies on underlying mechanisms, such as genetic, neurobiological, physiological, cognitive, emotional, behavioral and so forth. Development of questionnaires and interventions are also relevant. The translation is in the application of that basic science knowledge to the development of methods applicable to interventions and policies, culminating in pilot studies. This corresponds, in part, to Phase 1 and 2 NIH clinical trials research.


T2: Part of the "classical" step of research from bedside to practices and involves translation of program development to implementation under ideal conditions (efficacy trials) and scaling up to adaptable, generally randomized field studies in large defined populations (effectiveness trials).  The preventive intervention is first tested under ideal conditions. Then there is a transfer of the science to intervention practices and subsequent scaling up to larger and different patient populations, communities, schools, and other venues outside of the laboratory to determine whether they improve health and quality of life.  The translation, therefore, is from development, implementation and efficacy work to effectiveness trials. This type corresponds to Phase 3 and 4 clinical trials; they are combined given the equal importance of internal and external validity.


T3: Positive results from T2 then launches into T3, the practice-oriented phase involving field studies being translated to adoption and dissemination.  This phase also involves research to identify new clinical and scientific questions, barriers and gaps in service/program delivery, and how best to implement evidence-based programs in “real world” (i.e., clinical and community) settings.  The ultimate goal is to translate new evidence into adoption of evidence-based programs and practice guidelines and policies, as per T4. The translation is from effectiveness work to dissemination, implementation, adaptation and evaluation. This stage corresponds mostly closely with Phase 5 NIH clinical trials.


T4: Wide-scale, systematic dissemination, implementation, adoption and institutionalization of new guidelines, practices, and policies that emerge as the outcome of translation after research at the T4 level.  The effects of such changes in programs and policies need to be meticulously and critically evaluated, a process that will influence ways in which resultant practices are scaled up, adopted and sustained in various populations and settings.  The goal is to institutionalize evidence-based programming and effectuate lasting policy change. This stage represents a grossly understudied area of prevention. One of the few examples may be emerging in the near-future in tobacco regulatory science.

T5: Translation to global communities.  T4 results at the local and national levels eventually alter our universal understanding of the key determinants of health and well-being, constituting T5, last phase of translation.  This [now] commonly accepted knowledge leads to ways in which global policies and environmental change can effectively target those conditions to improve overall outcomes.  The ultimate goal is to reform social systems to become more responsive to human needs based on sound and well-tested scientific evidence, taking into account global political, economic, and cultural variations.