Overview

Translation. What is it, and why is it important? According to the 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 practice. For us, translational science:

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

Tufts CTSI supports the full spectrum of T1-T4 translational research focused on developing treatment, clinical practice, or changes in policy to improve health. We prioritize applied research involving the direct testing and/or evaluation of diagnostics, therapeutics, medical procedures, behavioral and other preventive interventions, and cognitive phenomena in people and their communities, or using materials of human origin such as tissues and specimens. 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.

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 testing in patient care into usual clinical care. These were referred to as the first and second blocks to translational research, “T1” and “T2” respectively, but soon it was appreciated that for maximal impact, these advances needed to be further translated, and “T3” and “T4” were articulated.

T1: From Bench to Bedside

T1 research translates promising laboratory and “pre-clinical” findings into the care of patients. Such studies might include first testing in humans, physiology, toxicity, and efficacy studies of promising treatments. T1 research yields knowledge that demonstrates potential strategies for diagnosis, treatment, and prevention.

T2: From Bedside to Clinical Practice

T2 research translates successful health application 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 discerning the appropriateness of treatments and tests in clinical care. T2 research yields knowledge about the efficacy of the 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 health strategies are applicable to the wide span of usual clinical care in practice. This might include clinical trials in broad ranges of settings and conditions and can also include creation of 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 is not part of the translational spectrum and focuses on identifying opportunities and potential approaches to health problems and includes a broad range of preclinical approaches employing animal models of human disease, human blood or cell lines, computational models, human physiological studies and non-interventional, correlational epidemiologic studies. Basic research yields knowledge about 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 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.

These guidelines defining the translational spectrum are based on the belief that authentic translational research requires a systems approach to the development of successful treatments and 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 health.

Defining Translational Research in Tufts CTSI Signature Program Areas

Comparative Effectiveness Research (CER)

CER is the generation and synthesis of evidence that compares the benefits and harms 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, 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 active partners in all aspects of research (identifying research needs and priorities, hypothesis development, study design, implementation, analysis, and/or results dissemination), not just as participants in studies based on affiliation or participation in a stakeholder or community group that is the target of 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

One Health Research

Translational One Health Research includes studies of naturally occurring diseases (not induced) shared by animals (domesticated not laboratory) and humans with the ultimate goal of improving human outcomes. This includes research involving animals with spontaneous 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.

Translational Research and 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 Signature Program areas, integrating special populations into research and/or the development of new translational research methods across the T1-T4 spectrum. Tufts CTSI does not fund basic research projects.

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 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.