The steps from translatable to translational research.

T he common justification for much research funding is that the outcomes will move from the laboratory to the clinic and patient care, or be converted into jobs and money. The term “translational research” is widely used in this context by medical research institutes and an increasing number of university departments to convey the message to politicians and taxpayers that research activities ultimately serve the public. The intense focus on translation is also a result of the NIH road map and former NIH Director Elias Zerhouni, who deliberated on how to achieve this goal [1,2]. However, in some cases, translational research is merely a label to attract financial support but in reality, it is not. A more analytical and stratified definition of “translation” would therefore provide greater transparency to a sector of research that heavily depends on public funding. It would also provide an instrument to understand better the nature of the research that is being undertaken in research institutes or university departments. Finally, anyone who is interested in an institute that claims to perform translational research would get an accurate picture of how that is being interpreted and carried out. As a starting point, it is useful to distinguish between translational research proper and translatable research: research that potentially could lead to translation. Indeed, there is confusion that comes from a lack of precision or a failure to classify activities correctly. Some of this arises from the frequent mixing of the terms “translational medicine” and “translational research”. A more detailed classification would therefore help to describe where a given project is placed along the chain of events from “translatable research” to “translational research”. For example, the Translational Research Working Group I at the NIH uses a single term, “basic science discovery”— which is also labelled at T0—for all activities prior to clinical research (http://www. cancer.gov/PublishedContent/Files/images/ trwg/TRWG_Oct06RT_ExSum_11-21-06.pdf; http://www.tuftsctsi.org/About-Us/What-isTranslational-Science.aspx?c=12904776559 4202220). A different approach by the Institute of Medicine’s Clinical Research Roundtable defines bottlenecks on the path to the clinic as T1—which prevent research findings being tested in the clinic—and as T2— which prevent the adoption of proven interventions as standard practice [3]. The common classification of translational research after T0 distinguishes four phases [4]. T1 is when a new treatment is first tested in humans in phases 1 and 2 clinical trials. T2 is when the results from a statistically relevant number of patients from phases 2 and 3 demonstrate the efficacy of the new approach. T3 is the phase when the new treatment is being tested more generally including phase 3 clinical trials. T4 is translating the findings from T3 into population health. Notwithstanding some of the ambiguities, this classification has helped to highlight the steps involved in translational medicine. The phase that is referred to as T0 has not benefitted from a similar definition, which has given rise to claims that research is translational when, in fact, it is translatable and often quite a distance away from translational medicine. To achieve some greater clarity, I propose a classification scheme that would help to define the steps in pre-clinical research from discovery to translation (Fig 1). Some obvious variations on the scheme could serve a similar purpose to classify research with the aim of commercialisation. Analogous to the four phases of translational research, it distinguishes four phases of discovery D1 to D4. D1 is pure basic research to gain knowledge. It is essential and the basis for the following stages, but does not itself focus on clinical use or any other application. This could, for example, include understanding fundamental aspects of cellular or molecular biology or developing algorithms to integrate complex data from different sources. D2 is disease-related research or oriented/ strategic research: the context is defined by a disease, and the work is designed to obtain new insight or a starting point for diagnosis, treatment or prevention. This could include, for example, genomewide association studies to search for disease-related genes, epidemiological studies to identify linkages between environmental factors and a disease, studies to establish a connection between imaging data and a disease or studies to correlate genomics or proteomics and a disease.