Abstract
Because translational research is not well defined, program developers are struggling to articulate specific program objectives, define the knowledge and skills (competencies) that trainees are expected to develop, develop an appropriate curriculum, and track outcomes to determine whether program objectives and competency requirements are met. Members of the Association for Clinical Research Training’s (ACRT) Evaluation Committee analyzed existing definitions of translational research and offered an operational definition for use in the educational framework. The authors argue in this article that translational research promotes the multidirectional and interdisciplinary integration of fundamental research, patient-oriented research, and population-based research, with the long-term goal of enhancing public health.
According to the authors, the approach to designing and evaluating the success of translational training programs must be flexible enough to accommodate the needs of individual institutions and individual trainees within the institutions, but it must also be rigorous enough to document that the program is meeting its short-, intermediate-, and long-term objectives, and that its trainees are meeting predetermined competency requirements. A logic model for evaluating translational research initiatives is presented.
The National Institutes of Health (NIH) has long funded fundamental and clinical scientist training in a range of fields. More recently, it has supported the training of scientists in translational research through the K30 and Clinical and Translational Science Award (CTSA) programs.1 Because basic and clinical research are clearly defined, developers of programs to train individuals in these types of research have been able to articulate program objectives, delineate the knowledge and skills (i.e., competencies) that trainees are expected to develop, and develop an appropriate curriculum. In contrast, since translational research is not well defined, program creators are dealing with some of these procedures.
As members of the Association for Clinical Research Training’s (ACRT) Evaluation Committee, we started to address this issue by analyzing the definitions of various forms of research. Then we created working definitions for translational research and related concepts. We describe our working definitions, examine their implications for educational training programs, and provide a framework to assist institutions in building program assessment procedures.
Basic Science and Basic Research Definitions
According to the American Cancer Society, basic science entails laboratory studies that lay the groundwork for clinical research.2 As one cancer center puts it, basic science entails gathering knowledge that is necessary for applying discoveries to patient care.3 However, when the director of the US Office of Scientific Development and Research proposed the establishment of the National Science Foundation (NSF) in 1945, he made the following distinction between b) basic science and c) basic science.
Basic research is conducted with little regard for practical outcomes. It provides broad knowledge as well as a comprehension of nature and its rules. This basic knowledge allows you to answer a wide range of critical practical questions, however it may not offer a comprehensive precise response to all of them. The goal of applied research is to give such comprehensive answers.
The NSF definition therefore specifies the primary goal of basic research as knowledge acquisition without the responsibility to apply it to practical objectives.
Medical colleges provide extensive basic research training. The fundamental scientific sector is highly established, with PhD programs available in subjects such as biomedical sciences, computational biology, and neuroscience. The fundamental sciences’ competencies have been explicitly defined, enabling for the successful construction and assessment of educational programs. Approximately 60% of the NIH funding is committed to fundamental research, with the majority of basic research expenditures going to PhD scientists.
Clinical Research Definitions
The National Institutes of Health Director’s Panel on Clinical Research established the following three-part definition of clinical research in 1997:
- Patient-centered study. Human subjects research (or research on human-derived materials such as tissues, specimens, and cognitive processes) in which an investigator (or colleague) directly interacts with human subjects. In vitro experiments that use human tissues that cannot be connected to a live person are excluded from this classification. Patient-centered research encompasses (a) human illness processes, (b) therapeutic approaches, (c) clinical trials, and (d) the creation of novel technologies.
- Epidemiologic and behavioral research.
- Research on outcomes and health services.
The NIH established the Clinical Research Curriculum Award in 1998 to “improve the quality of training in clinical research.” This award financed over 50 training programs, several of which give degrees in clinical research.
The National Institutes of Health’s definition of clinical research has been broadly recognized by institutions and programs, and it serves as a common foundation for NIH-funded clinical research training programs. The concept has aided cross-program attempts to define core competences, best practices, and meaningful outcomes applicable across the vast range of clinical research training. As a result, program evaluators have been able to construct appropriate evaluation measures for documenting the performance of training programs.
Today, around 30% of the NIH funding is spent on clinical research.5 However, some feel that this statistic includes animal model studies, in which case true support for clinical research would be significantly lower.
Translational Research Definitions
Translational research has a more ambiguous meaning than fundamental and clinical research.
Although a Medline search shows that the word translational research first emerged in 1993, there were few references to it in the medical literature throughout the 1990s, and the most of them related to cancer research. Previously, the term translational research was used in the cancer literature to refer to work spanning different types of research (e.g., immunology studies spanning basic and clinical research) or work spanning disciplines within a specific type of research (e.g., bench research involving molecular genetics and immunology). Today’s literature has a variety of efforts to define the word in numerous fields.
The NIH provided the following definition in a recent statement regarding applying for a CTSA:
Translational research is divided into two categories. One is the process of translating findings made in the laboratory and in preclinical investigations into clinical trials and studies in people. The second area of translation study is concerned with improving community acceptance of best practices. Translational research also considers the cost-effectiveness of preventative and treatment strategies.
Translational research, according to this definition, is part of a unidirectional continuum in which research results are carried from the researcher’s bench to the patient’s bedside and community. The first step of translational research (T1) moves information from fundamental research to clinical research, and the second stage (T2) moves results from clinical studies or clinical trials to practice settings and communities, where they enhance health.
Steven Woolf noted in a 2008 article that “translational research means different things to different people”(p211) and claimed that the many forms of translational research are too narrowly defined. He stated, in particular, that if T2 research is to provide the information required to enhance health and quality of life, T1 research must integrate population sciences (e.g., epidemiology, psychology, economics, and behavioral sciences).
The Clinical Research Roundtable, convened by the Institute of Medicine (IOM), created a paradigm for translational research that was closely compatible with the NIH definition.
The National Cancer Institute (NCI) Translational Research Working Group, like the NIH and the IOM, included both basic and clinical research in the T1 segment of the continuum: “Translational research transforms scientific discoveries arising from laboratory, clinical, or population studies into clinical applications to reduce cancer incidence, morbidity, and mortality.”12 However, given that basic and clinical research involve inherently different knowledge s,
A Model for Designing and Evaluating Translational Research Programs
Our purpose as members of the ACRT Evaluation Committee was to provide a framework for evaluating translational research initiatives. We rapidly understood, however, that differences over what is and is not included in the concept of translational research would make defining competence criteria and determining compliance problematic. As a result, we started debating the above-mentioned definitions. We also looked at papers on the issue of translational research as well as data from the first 12 CTSA grantees’ websites.
Definitions in use
The following is our working definition of translational research:
Translational research promotes the multidirectional integration of fundamental research, patient-centered research, and population-based research, with the long-term goal of enhancing public health. T1 research accelerates the transition from fundamental to patient-oriented research, resulting in new or better scientific knowledge or standards of treatment. T2 research enables the transition from patient-oriented to population-based research, resulting in better patient outcomes, the application of best practices, and improved community health. T3 research encourages collaboration between laboratory-based and population-based research in order to advance scientific knowledge of human health and illness.
We feel that seeing T1 as the process of shifting from bench to bedside reflects progress toward the aim of greater health. It may conjure up images of patients getting medical treatment or of healthy people benefitting from advancements in health care or public health. Alternatively, it might imply that patient-centered research (research at the bedside) is an important step toward better illness treatment or prevention.
We propose a model (see Figure 1) that represents the dynamic interaction inherent in the idea of translational research. The circular form of the model implies that research is a continuous cycle, and the bidirectional arrows underline that new knowledge and hypotheses are created at each phase. Some fundamental research and population-based research are translational, although neither is by definition translational. Patient-oriented research, on the other hand, focuses on challenges that have the potential to transfer into clinical practice and so influence health. For these reasons, the model only incorporates a portion of fundamental research and population-based research inside the circular framework, but it includes all patient-oriented research.
The Evaluation Committee of the Association for Clinical Research Training presented a model for translational research.
The idea of fundamental research, as described previously, is widely accepted. The NIH defines clinical research as including the principles of patient-oriented research and population-based research. We define patient-oriented research as studies that include groups of patients or healthy individuals and are designed to understand disease and health mechanisms, determine the effects of a treatment, or provide a decision analysis of patients’ care trajectories.16 Clinical trials are an example of patient-oriented research that has the potential to directly affect clinical practice. Population-based research encompasses studies including epidemiology, social and behavioral sciences, public health, quality assessment, and cost-effectiveness.
The T1, T2, and T3 arrows in our model depict transitions from one sort of study to another. Drug development, pharmacogenomics, and certain investigations of disease causes, as well as research into new fields such as genetics, genomics, and proteomics, are examples of T1 research. Clinical epidemiology, health services (outcomes) research, and the newly evolving approach of community-based participatory research are examples of T2. Emerging fields such as molecular and genetic epidemiology are examples of T3. T3 study, for example, demonstrates how population research feeds theories that may be validated in basic science labs, and how biomarkers in animal models can be translated into population-based screening tools.
Implications for training program design
To transfer information from one sort of study to another (for example, to take a fundamental science discovery to the bedside), numerous disciplines must interact. Collaboration across disciplines, as facilitated by multidisciplinary teams, promotes the formation of fresh thoughts and ways to solving critical health challenges. The emergence and development of new ideas are aims of translational research, and there are several training programs that may give an academic road to these goals.
Training in translational research will differ based on the trainees’ backgrounds and the fields of research they choose to pursue. Given the variety of educational backgrounds and research interests, practically every trainee will need a unique program. Trainees who have focused on basic laboratory research will need to become immersed in clinical sciences and clinical practice to ensure an understanding of complementary disciplines and to improve communication and collaboration, while trainees with a clinical focus will need to gain exposure to basic science research. Both sorts of people will benefit from population-based scientific training, which is supported, for example, by the Burroughs Wellcome Fund, which funds the Institutional Program Unifying Population and Laboratory Based Sciences.
The specifics of a clinical immersion experience will be determined by the study area of interest. Trainees interested in neuroscience, for example, may prefer to follow physicians in a psychiatry or neurology clinic, while trainees interested in bone tissue regeneration may wish to engage in the activities of a clinical orthopedic surgery program. Trainees interested in laboratory immersion might attend courses in molecular biology or genetics and work at the bench for 3-4 months. Trainees interested in health care research who have a background in the social sciences or economics may need to join a team of investigators working in their field.
Fundamental training in study design, data collection, statistical analysis, ethics and research integrity, human subject protection, the search for funding sources, the writing of institutional review board protocols and grant applications, the pursuit of patents and technology transfer, and government requirements for new drugs and devices could benefit all trainees. Because of the nature of translational research, training programs must also guarantee that trainees gain the skills required to succeed in a diverse collaborative team. Communication and negotiating abilities, as well as ethical and humanitarian attitudes, are examples of these competences.
The most successful strategy would be to create a personalized curriculum for each trainee, coordinated by a learner-centered advisory council comprised of mentors with diverse and complementary experiences in clinical practice and fundamental and clinical research. To guarantee coordination of efforts and the effectiveness of the mentoring process, one of the mentors would take on the position of main mentor.
Mentoring is a demanding but highly rewarding endeavor whose success is dependent on the vastly different skills, needs, and attitudes of different individuals.18 Mentors who can monitor the incorporation and understanding of translational research essentials will be critical to the positive outcomes of training programs. Trainees will, however, need to have critical thinking abilities as well as practical experience on how to work collaboratively and lead teams. Although most medical schools recognize the importance of teaching students to think critically as Jerome Groopman points out, the older generation of students were not taught to think as clinicians. Although recent emphasis has shifted to training medical students and residents how to follow preset algorithms and decision trees, these approaches are challenging when clinicians need to think outside their domains.
Historically, medicine has maintained a hands-off approach to teaching management and leadership, assuming that learning to manage and lead is simply instinctive. “Something about management looks so easy that we…never doubt that we could succeed where others repeatedly fail,” says Thomas Teal, former senior editor of the Harvard Business Review.(pp3-4) Because managing is less a series of technical tasks and more a set of human interactions, managers and team leaders require what Daniel Goleman and his colleagues call “emotional intelligence” and other skills that are not typically taught in research training programs. We typically go to engineers and designers to learn about innovation and creative problem solving.
Similarly, when we think about management, we often look to the business sector. Explicit training of fellows and younger faculty in critical thinking, leadership, and management skills is a good strategy to create a supportive atmosphere that develops critical thinking, leadership, and management abilities.
To guarantee comprehension across disciplines, a good translational research training program must integrate established curriculum features in novel ways. It must also develop and implement new curricular elements and approaches to ensure that its trainees can critically examine the research process, think “out of the box” to develop ways to impact health care by transferring knowledge from and to the bench, bedside, and community, engage in multidisciplinary collaboration, understand successful approaches to community engagement, and develop appropriate techniques to manage multidisciplinary research. The translational researcher will be able to conceive and operate in an integrated interdisciplinary way using multidisciplinary talents, and will become a new sort of investigator.
Meeting these objectives is difficult since research training programs are not typically content-based. We must explore encouraging the use of problem-based learning24,25 as a doorway to collaborative leadership in order to create a community of learners and leaders. Adopting these strategies would need a cultural shift in medical schools, but the time has come to start the process if we want to take a step forward in improving the practice of going from bench to bedside to community and back in translational research.
An assessment strategy
Because translational research requires customized training, the method to assessment must be adaptable. One of the most adaptable techniques is to create a logic model that provides a visual representation of the links between program parts, goals, and expected results in the short, middle, and long term. The accompanying logic model (List 1) is an example of a framework for a translational research training program. The logic model technique has the benefit of being adaptive when study definitions and research aims change. Specific aspects of the model, as well as indicators and data sources, may be changed without disturbing the overall logical flow of goals.
The domains to be evaluated in the logic model for a translational research program could include (1) whether the tools used to achieve predetermined objectives, including general and scientific area specific competencies in translational sciences, are adequate; (2) whether the trainees acquire the cognitive and practical skills required to effectively conduct translational research; and (3) whether the trainees are successful in developing and pursuing a translational research project. The outcomes of each of these domains could include: (1) evidence that the program’s courses, seminars, workshops, and laboratory experiences lead to the fulfillment of predetermined competency requirements; (2) evidence of improvement over time in trainees’ knowledge and skills regarding translational research topics and endeavors, as measured by testing and evaluations provided by scientific advisory committees; and (3) evidence of successful career development.
Conclusion
We think that translational research includes cooperation among scientists from several disciplines and travels bidirectionally from one form of study to another—from fundamental research to patient-oriented research, population-based research, and back. The design of an effective translational research training program is difficult because the program must provide each trainee with the chance to acquire a mix of abilities that are not taught simultaneously in typical training programs. The approach to evaluating the success of translational training programs must be flexible enough to accommodate the needs of individual institutions and trainees within those institutions, but it must also be rigorous enough to demonstrate that the program is meeting its short-, intermediate-, and long-term objectives and that its trainees are meeting predetermined competency requirements. These assessment attempts may benefit from a logic model architecture with proper domains.
