1. Definition
According to the University of California, Davis, translational research is “the process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs to improve health outcomes. It’s often described as ‘bench to bedside’ bridge” 1.
2. Multidisciplinary collaboration
In translational medicine (TM), collaboration with different disciplines is very important 1. Integration and partnership of basic, clinical, practice, population, and policy‐based research are key 1. This results in creating knowledge to answer complex and unsolved medical questions 1. TM incorporates different experts from different biomedical and associated sciences or disciplines with emerging technologies 2. This aims to promote advancements in global healthcare through translational approaches as well as through the development of guidelines, tools, medical knowledge, expertise, products, pharmaceuticals and procedures 2.
3. Translational versus applied sciences
According to Prof. Elaine Wethington, from the Departments of Human Development and Sociology at Cornell: “applied research is any research that may possibly be useful for enhancing health or well‐being. It does not necessarily have to have any effort connected with it to take the research to a practical level. For example, an applied research study might analyze longitudinal data that tracks participants’ health and social relationships. The researchers would report their findings in an academic journal. But in translational research, the same study would include some “action steps.” The researchers would partner with a community and ask for ideas about how their findings might apply there. Together, they would come up with an intervention plan that would also include scientific evaluation of its effectiveness.” 3.
4. Translational versus comparative medecine
According to the American Veterinary Medical Association (AVMA) 4: “Comparative medicine is a discipline in which the similarities and differences in biology among animal species are studied to enhance the understanding of mechanisms of human and animal disease. Comparative medicine facilitates the translation of basic science knowledge into clinical applications”.
5. Patient-oriented research
The primary goal of TM is the integration of the corresponding findings and capabilities for optimizing patient outcomes, prevention, screening and therapy of disease and improving health policy 2.
6. Translational phases and methodology 5
The different stages of translational research as well as the associated methodologies are described below. There are five different stages, i.e. T0, T1, T2, T3 and T4.
T0: Basic and applied science research: Defining mechanisms and targets: basic research, animal research, preclinical and preintervention studies.
T1: Translation to humans: Discovery of application to human health: proof of concept, early stage human clinical trials.
T2: Translation to patients: Discovery of application to clinical settings: later stage human clinical trials, efficacy studies, controlled observational studies, clinical guidelines.
T3: Translation to practice: Health application of evidence‐based practice guidelines and practice guidelines to health practice: effectiveness research, CER, D&I research, health services research.
T4: Translation to communities: Health application of practice to population health impact: D&I research, scale‐up and spread research, population health impact.
The methodologies associated with the different stages are:
i. Pre-intervention research: Associated with T0 and T1 stages. The research done in a controlled laboratory setting, using nonhuman subjects. The goal is to understand the cellular and molecular mechanisms of a disease process.
ii. Efficacy research: Associated with T2 stage. It includes highly controlled clinical research that is linked with internal validity. Homogeneous samples and controlling intervention parameters reduce the threats to causal inference. The primary outcome measures target individuals and are symptom specific.
iii. Effectiveness research: Associated with T3 stage. It includes clinical or community research that is primarily concerned with external validity. Using heterogeneous samples in “real‐world” and different study locations reduce the threats to generalizability. The main outcomes range from clinical to other individual and organizational‐level outcomes.
iv. Dissemination research: Associated with T3 and T4 stages. It consists on spreading evidence‐based interventions to a specific audience using planned strategies and examining the success of this spread. The main outcomes target individuals and/or organizations, such as awareness, receipt, acceptance, and use of information.
v. Implementation research: Associated with T3 and T4 stages. It consists on using evidence‐based interventions and examining whether the interventions are put into place as designed. This research uptake clinical interventions by providers and/or systems of care, with primary outcomes such as levels and rates of adoption, fidelity, implementation costs, and sustainability.
vi. Scale-up and spread research: Associated with T4 stage. It “Deliberate efforts to increase the impact of health service innovations successfully tested in pilot or experimental projects so as to benefit more people and to foster policy and program development on a lasting basis.”
7. Trial types
Four types of trials are existing in translational research 5:
i. Hybrid type trials: Focuses on the assessment of clinical effectiveness and implementation. It can adopt three approaches: (a) testing effects of a clinical intervention on relevant outcomes while gathering information on implementation; (b) dual testing of clinical and implementation strategies; (c) testing of an implementation strategy while gathering information on the clinical intervention’s impact on relevant outcomes.
ii. Clinical effectiveness trials: test the clinical intervention with the unit of randomization and unit of analysis at the patient or clinical unit level.
iii. Implementation trials: is the implementation of an intervention strategy with the unit of randomization and unit of analysis at the provider, clinical unit, or system level. Primary outcomes are focused on the adoption and uptake of the clinical intervention as well as process/ quality measures.
iv. Pragmatic or practical clinical trials: are clinical trials where the hypothesis and study design are developed to answer the questions faced by decision‐makers. The characteristic features include: (a) clinically relevant alternative interventions to compare, (b) diverse population of study participants, (c) participants from heterogeneous practice settings, (d) data collected on health outcomes.
REFERENCES
1. Translational research. University of California, Davis Available at: https://www.ucdavis.edu/one‐health/translational‐research/. (Accessed: 1st December 2019)
2. Cohrs, R. J. et al. Translational Medicine definition by the European Society for Translational Medicine. New Horizons Transl. Med. 2, 86–88 (2015).
3. Wethington, E. What is translational research? Departments of Human Development and Sociology, Cornell Available at: https://evidencebasedliving.human.cornell.edu/2010/08/18/what‐is‐translationalresearch/. (Accessed: 1st December 2019)
4. AVMA. Comparative Medicine and Translational Research. American Veterinary MedicalAssociation Available at: https://www.avma.org/KB/Policies/Pages/Comparative‐Medicine‐and‐Translational‐Research.aspx. (Accessed: 1st December 2019)
5. Zoellner, J. M. & Porter, K. J. Translational Research : Concepts and Methods in Dissemination and Implementation Research. in Nutrition in the Prevention andTreatment of Disease 123–144 (Elsevier Inc., 2017). doi:10.1016/B978‐0‐12‐802928‐ 2.00006‐0