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- Anthony N. DeMaria, MD, MACC, Editor-in-Chief, Journal of the American College of Cardiology∗ ()
- ↵∗Address correspondence to:
Dr. Anthony N. DeMaria, Editor-in-Chief, Journal of the American College of Cardiology, 3655 Nobel Drive, Suite 630, San Diego, California 92112
For most of my 30-plus years in cardiology I have considered myself a clinical investigator. Following an early career that dealt almost exclusively with patient-based research, I turned to the animal laboratory after becoming more involved with technology. Although working with a variety of experimental protocols, all were directed toward human disease, and I knew for sure that I was not a basic scientist. Then, several years ago, through reading and at meetings, I learned that translational research was the “wave of the future.” The National Institutes of Health (NIH) had established the Clinical and Translational Science Award (CTSA) program, and a number of very wise people strongly encouraged me to direct my investigative efforts toward translational research. Although I was ready and willing to do so, only one problem existed: no one could give me a precise definition of exactly what translational research was.
The term “translational research” first appeared in PubMed in 1993, and it has become increasingly common in that venue since 2000. It has been written repeatedly that translational research lacks a clear definition, and that if you ask 10 people you will probably get 10 different responses (1–3). In its simplest form, translational research represents a fundamental concept that I have encountered since entering medicine: the conversion of discoveries from “bench to bedside.” However, this concept is all-encompassing and non-specific. According to the Merriam-Webster dictionary, translational medical research is “concerned with facilitating the practical application of scientific discoveries to the development and implementation of new ways to prevent, diagnose, and treat disease” (4). The universal bible of information, Wikipedia, defines it as “scientific research that helps to make findings from basic science useful for practical applications that enhance human health and well-being” (5). However, all of these definitions are non-specific, and as is so often the case, the devil is in the details.
An attempt to more exactly specify the components of translational research is complicated by uncertainty regarding the nature and boundaries of other terms used to characterize investigation. Thus, one can read that translational activities serve as a bridge between basic (sometimes called fundamental) and applied research, but the definition of these entities is not necessarily precise. For example, one definition states that fundamental research is driven by scientific curiosity and does not necessarily have any obvious practical value (2). However, I doubt that many of my colleagues who consider themselves basic scientists would fully agree with that description. Other terms that are frequently encountered are pre-clinical and clinical research. It is not clear, though, if pre-clinical research is basic or applied. Neither, in my view, is there universal agreement as to whether health services and cost-effectiveness studies are included in clinical research. Finally, some descriptions of translational activities focus on the development of products and bringing them to the market. This clearly represents an extremely focused notion of what constitutes translational research.
In an attempt to bring some clarity to the concept of translational investigation, the Institute of Medicine convened a Clinical Research Roundtable. This group identified 2 “translational blocks,” termed T1 and T2, that existed in the research enterprise and could form the basis of a more detailed definition of translational research (1). T1 consisted of a block in “the transfer of new understandings of disease mechanisms gained in the laboratory into the development of new methods for diagnosis, therapy, and prevention and their first testing in humans.” T2 was described as an obstruction to “the translation of results from clinical studies into everyday clinical practice and health decision making.” Studies aimed at overcoming T1 and T2 blocks would therefore constitute translational research. Roughly, T1 could be viewed as patient-oriented research and T2 as population-based investigation. Nevertheless, it remains uncertain how nonhuman research with clinical implications is classified.
To a certain extent, the concept of translational investigation could be seen as old wine in new bottles. The attempt to develop a clear new concept is impacted by the fact that the path from basic science discovery to full incorporation into daily clinical medical practice is a continuum. The National Cancer Institute has portrayed the process in steps designated as basic science discovery, early translation, late translation, dissemination, and adoption. So, it appears that the vast majority of biomedical research currently being performed could fit somewhere in this spectrum. It seems to me that basic scientists have always had a keen focus on any potential clinical implications of their experiments and findings. Similarly, clinical investigators have always been searching for new innovations that could be applied to human health. With the recent emphasis upon cost containment and outcomes, studies directed at these issues have increased dramatically. So, although much of the current research may not bear the designation “translational,” it is likely that it is accomplishing the same goal.
My previous comments are not meant to diminish the need that exists to convert basic biological discoveries into preventive, diagnostic, or therapeutic modalities to improve human health. Whether counting new patents or new drugs/devices approved for patient care, a consensus exists that there has been a significant disproportion between the large number of new basic science insights and mechanisms and the relatively small number of new modalities that benefit patients (1–3,6). As expressed by 1 observer, the NIH is the National Institutes of Health, not the National Institutes of Biomedical Research (3). Of perhaps even greater importance, there is a pressing need to educate and train clinical investigators to be able to provide the expertise to transform basic science breakthroughs into better human health. If conceptualizing the effort to meet these needs under the rubric of translational research helps to accomplish this goal, then the lack of clear definition may be a small price to pay.
It has occurred to me that there may be an alternate approach to bridging the chasm between basic and clinical investigation. Rather than create a new entity of uncertain definition called “translational research,” perhaps new and existing studies could be graded on the degree to which they are translational. Basic fundamental findings that have no immediate implications for human health would have a very low grade. Pre-clinical experimental studies directed toward conversion to clinical application would receive good grades. Initial human studies to test the safety and efficacy of novel drugs or methods and provide the crucial link between the bench and the bedside would garner the highest grades. If the desire is to emphasize investigation that transforms basic discoveries into clinical modalities, resources could be allocated based upon the degree to which a project was “translational.”
The deficit in the conversion of basic science discoveries to novel approaches that improve human health generated the concept of, and emphasis upon, translational research. At present, the definition of translational research appears to reside in the eye of the beholder. This is analogous to pornography: although I cannot precisely define it, I know it when I see it. The problem lies not in the overall concept, but in the specific details. Despite this lack of clarity, huge NIH programs, such as CTSAs, medical school units, and new medical journals, have all been created that are dedicated to translational research. In fact, translational research may have received more attention and more resources than any other entity without exact definition in the history of medicine. Nevertheless, the issue that it addresses is serious, pressing, and most worthy of the effort and attention. I believe that, rather than create a new entity whose definition is not agreed upon, it would be better to classify investigation into the well-characterized and accepted existing categories and to assess each project based upon the degree to which it was translational. However, that, like most things about translational research, is just one man's opinion. Regardless of how the field evolves, for the foreseeable future whenever I hear the term I guess I will continue to have the same response: “What do you mean by translational research?”
- American College of Cardiology Foundation
- ↵Merriam-Webster. Translational research. Available at: http://www.merriam-webster.com/dictionary/translational%20research. Accessed November 22, 2013.
- ↵Wikipedia. Translational research. Available at: http://en.wikipedia.org/wiki/Translational_research. Accessed November 22, 2013.