Overview

As defined by the NIH National Center for Advancing Translational Sciences (NCATS):

Translation is the process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and populations – from diagnostics and therapeutics to medical procedures and behavioral interventions.

Tufts CTSI focuses on translating research into impact on health. This means, translational science:

  • Connects biomedical and clinical studies to changes in clinical practice, the health of communities, and health policy, with the clear objective of having a positive impact on health.
  • Is patient- and population-oriented, so the public gets a significant return on investment.

Defining the Translational Spectrum for Tufts CTSI

In creating the NIH CTSA program, “clinical and translational science” was advanced by NIH Director Elias Zerhouni to address “translational blocks,” or impediments to the translation of basic research into improvements in health. The initial focus was on the translation of bench research into demonstrated effects for patients, “bench-to-bedside” translation, and also on translation from studies examining approaches to improve patient care into usual clinical care. These were referred to as the first and second blocks to translational research, “T1” and “T2” respectively. It also has been appreciated that for maximal impact, these advances needed to be further translated, and “T3” and “T4” were articulated.

Tufts CTSI also recognizes a critical step from pre-T1 research into initial human studies, which we call T.5 research. T.5 research focuses on incorporating clinical insights into the full span of preliminary research and development (R&D) and connects basic research on diseases with human medicine.

Tufts CTSI supports the work of researchers across the full spectrum of T.5-T4 translational research, focused on developing treatments, clinical practice, or changes in policy to improve health. We prioritize applied research involving the direct testing and/or evaluation of diagnostics, therapeutics, devices, medical procedures, behavioral and other preventive interventions in people and their communities, or using materials of human origin such as tissues. Translational research can also encompass research on naturally occurring diseases shared by animals and humans, human-animal interactions, the intersection of human/animal/environmental health, and the treatment or prevention of zoonotic diseases.

T.5: Bridging Pre-clinical Development to Initial Human Studies

T.5 research focuses on turning concepts into testable prototypes and seeks to de-risk translation by accelerating iterative R&D cycles. By using pre-clinical data to fine-tune early testing and design sequences, promising ideas are more likely to reach medical application. Successfully traversing this translational step requires specialized facilities and tools, and close collaboration between scientists, engineers, biomedical researchers, and clinical care providers.

T1: From Bench to Bedside

T1 research translates promising laboratory and pre-clinical findings into the care of patients. The goal of T1 research is to test the utility of a diagnostic or effects of a treatment or prevention intervention in humans. Such studies might include novel methods of diagnosis, proof-of-concept, and first testing in humans for promising physiology, toxicity, pharmacokinetics treatments, and other preliminary efficacy studies. T1 research yields knowledge that demonstrates potential strategies for diagnosis, prevention, and treatment.

T2: From Bedside to Clinical Practice

T2 research translates successful applications in humans into wider use in clinical practice in patient populations, and includes controlled observational studies and clinical trials, survey research, and other approaches to further define the appropriateness of treatments and tests in clinical care. T2 research may yield knowledge about the efficacy of various interventions in optimal clinical settings.

T3: From Clinical Practice to Widespread Clinical Practice and Care Delivery

T3 addresses the need to understand whether treatments, diagnostic tests, or other interventions are generalizable to the wider span of clinical practice. This might include clinical trials in broad ranges of settings and conditions and can also include evidence-based guidelines for improved health care delivery, dissemination strategies, and widespread implementation of care strategies. T3 research yields knowledge about how interventions work in real-world settings.

T4: From Health Care Delivery to Community, Public Health, and Public Policy

T4 research translates effective health care delivery into improved community and population health, informs new policies, and includes outcomes research, population monitoring, the wider dissemination/implementation of improved practices/interventions, and health policy. T4 research yields knowledge that ultimately results in improved world-wide health.

Basic Research: Pre-Translational Research

Basic research (earlier than T.5), while a critically important foundation for translational research, is not part of the translational spectrum and focuses on gaining greater knowledge and understanding of the fundamental mechanisms of biology, disease, or behavior. Basic research identifies opportunities and potential approaches to health problems and includes a broad range of approaches employing animal models of human disease, research in tissue culture cell lines, computational models, human physiological studies, and non-interventional, correlational epidemiologic studies. Basic research yields knowledge about basic biological, social, and behavioral mechanisms and presentations of human disease.

For Tufts CTSI, the following areas are considered basic research and are NOT translational:

  1. Research solely conducted in model organisms, even with a clear human disease analog.
  2. In vivo or in vitro research on disease mechanisms conducted in transgenic animals or cell lines expressing human genes, even with a clear human disease analog.
  3. Research involving human xenografts, unless targeted to the treatment a specific human disease or condition.
  4. Research on human-derived tissue culture cell lines.
  5. Computer-assisted simulations of drug, device, or diagnostic interactions within living systems.

At Tufts CTSI, we believe authentic translational research requires a systems approach to the development of successful treatments and that it bridges the gap between discoveries at the molecular or component level and interventions at the organism or organization level. Translational research should focus on applied research projects which turn findings from the laboratory, clinic, and community into treatments and interventions with the clear potential to have a significant impact on the health of the public.

Defining Translational Research in Tufts CTSI Priority Program Areas

Comparative Effectiveness Research (CER)

CER is the generation and synthesis of evidence that compares the risks and benefits of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care. The purpose of CER is to assist the public, participants, clinicians, purchasers, payers, and policy-makers to make better informed decisions that will improve health care for individuals and populations.

Stakeholder and Community-Engaged Research (SCE)

includes stakeholders and/or community members as authentic and active partners in all aspects of research. This includes: identifying research needs and priorities, hypothesis development, study design, implementation, analysis, and/or results dissemination. Research that only includes participants based on affiliation or participation in a stakeholder or community group that is the target of research is not considered stakeholder- and community-engaged research. Stakeholders include (7 Ps of Stakeholders):

  1. Patients, their families, communities, and the public
  2. Providers
  3. Purchasers
  4. Payers
  5. Policy makers
  6. Product makers
  7. Principal Investigators

Integrating Special Populations

addresses health disparities or translational research gaps involving: 1) children, 2) elders, 3) minority or underserved populations (e.g., differences in racial, ethnic, gender, or socio-economic status); 4)people living in rural vs. urban environment; and 5) pregnant women; 6) survivors of childhood diseases that are transitioning to adult care; 7) people with disabilities; and 8) “hard-to-reach” groups that are often impacted by health disparities.

One Health Research

Translational One Health Research includes studies of naturally occurring diseases (not induced) shared by animals (wild or domesticated, not laboratory) and humans with the ultimate goal of improving human outcomes. This includes research involving animals with naturally occurring disease that serve as models of comparable human disease, research on human-animal interactions (e.g., animal-assisted therapy, pet ownership) as it relates to the physical and mental health of humans, intersections between human/animal/environmental health, and study of the treatment or prevention of zoonotic diseases transmitted between wildlife or domesticated species and humans.

Basic One Health Research, which may have implications for human health, but does not focus on developing treatment, clinical practice, or changes in policy to improve human health, is not considered translational.

Defining Translational Research Methods for Tufts CTSI

Translational Research Methods include procedures, techniques, and tools for approaching and solving translational research questions, problems, or barriers.

Tufts CTSI supports the development of generalizable and broadly applicable methods that allow researchers to:

  • Overcome roadblocks that impede the conduct of clinical and translational research.
  • Expedite translation of biomedical discoveries into interventions.
  • Improve efficiency and quality across the translational research spectrum.

Clarifying What Translational Research Means for the Tufts CTSI Pilot Studies Program

 

Prioritizing Pilot Studies Program Goals

The Tufts CTSI Pilot Studies Program “seeks proposals for innovative, high impact, translational science projects with a focus on building interdisciplinary, multi-institutional research teams including investigators from the basic, clinical, and/or applied sciences.” Applicants are strongly encouraged to focus on one of our Priority Program areas, integrating special populations into research and/or the development of new translational research methods across the T.5-T4 spectrum.

A clear focus on funding high-impact, authentic translational research, as opposed to basic research, is critical for Tufts CTSI not only because it is consistent with the NCATS vision for the program, but also because it supports our mission “to stimulate and promote innovative clinical and translational research, with the goal of improving the public’s health.” The Tufts CTSI Pilot Studies Program will be successful if it:

  1. Initiates translational research in Tufts CTSI priority program areas
  2. Builds new interdisciplinary, multi-institutional research teams
  3. Generates preliminary data for subsequent translational grant submissions to external funding agencies
  4. Disseminates research findings, both positive and negative, through publications, presentations, educational materials, training, etc.
  5. Applies findings to patients and populations in the form of new interventions, treatments, devices, practices or policies and demonstrates a measurable impact on health.