Bench to Bedside - Translational Medicine Flashcards
What is translational medicine?
The process of turning observations in the laboratory, clinic and community into interventions that can improve the health of individuals and the public.
From diagnostics and therapeutics to medical procedures and behavioral changes - national center for advancing translational sciences.
What coordinates translational medicine in the USA and Australia?
NIH in USA
NHMRC in Australia
What are the stages of translational medicine? How is the stage progression between stages?
Spectrum from T0 to T4
T0 = basic biomedical research
T1 = translation to human
T2 = translation to patients
T3 = translation to practice
T4 = translation to communities
Not a linear progression of one stage to the next
Each step feeds back on the previous stages, translating basic discoveries all the way up to population health, implementation and improvement, gaining insights that can be applied backwards and forwards
What kind of research is done in T0?
Preclinical and animal studies. Defining mechanisms, targets, and lead molecules.
What kind of research is done in T1?
Proof of concept in phase 1 clinical trials. New methods of diagnosis, treatment, and prevention.
What kind of research is done in T2?
Phase 2 and phase 3 clinical trials. Controlled studies leading to effective care.
What kind of research is done in T3 and T4?
Implementation research. In these stages data is translated into practice and community allowing for delivery of recommended and timely care to the right patient to create a true benefit to society.
What is the purpose of T0, T1, and T2?
Translation from basic science to human studies.
What is basic science research?
Fundamental or “bench” research.
It is the foundation for all subsequent stages of research
In this stage basic research involves exploration that can reveal fundamental mechanisms of biology, disease or behaviour.
Every stage of translational research spectrum builds upon and informs basic research.
How is basic science research translated to humans (T1)?
Using discoveries on human cells/tissues or other human models pre-clinically.
Example of this is testing a new anti-cancer drug on tumour cells in a petri dish
How is clinical data translated to patients (T2)?
Movement of discoveries into patients via clinical trials.
What does clinical research include?
Clinical research includes;
Studies to better understand a disease in humans, and to relate these findings to observed in animal or cell models of the disease.
Testing new treatments for toxicity and efficacy on healthy people and ill people for whom no other treatment exists.
Behavioural and observational studies
Testing new treatments for toxicity and efficacy, on healthy people and ill people for whom no other treatment exists.
How can information be translated to practice after translation to humans and patients? (T3)
Involves adoption of interventions that have been demonstrated to be useful in research setting into routine clinical care for the general population.
Also includes evaluation of the results of clinical trials and to identify new clinical questions and gaps in care.
What kinds of therapies emerge at the T3 stage?
Therapies that emerge from the Dr’s office:
Pregnancy testing
Genetic testing
New drugs
New diagnostics, imaging and medical devices
Example of question asked in the T3 stage:
What is the proportion of women who meet the family history criteria are tested for BRCA and what are the barriers to testing?
How is research translated to the community? (T4)
Public health implementation
Researchers study health outcomes at population level to determine the effect of disease and efforts to prevent diagnose and treat them.
Findings help guide scientists to assess the effects of current interventions and to loop back and develop new and better ones.
Example of question asked in T4 stage:
Does BRCA testing in asymptomatic women reduce breast cancer incidence or improve outcomes?
What are the most important barriers to translational research?
Clinical research efficiency
Collaborations and partnerships
Data transparency and release - effective dissemination
De-risking therapeutic development
Predictive efficacy and toxicology
Why is clinical research inefficient?
Clinical translation research is often a very slow process because it takes time to develop ideas and to test them. It also takes time to build a team with the appropriate expertise to progress them.
Why is collaboration and partnership a barrier to translational research?
It is essential for collaboration to occur which means there is a need for partners that understand how to progress ideas and trials.
Different skills are needed such as surgeons, data analysts, physicians, scientists, policy makers, public health advocates, etc…
Collaborations are the cornerstone of translational science and if they don’t work they will slow down translation at every stage
Why is effective dissemination such a hurdle to translational research?
Attention needs to be paid to the full and effective reporting of research results
Without good data, it’s impossible to build good research and effective therapies to make change.
Data needs to be made publicly available to spur innovation and discovery
Efforts need to be made to enable the release of methods and data from all stages of research
What are the risks associated with moving through each stage of the translational pathway?
Will the new idea still work
Who will fund it?
How long will it take?
Etc
What are the barriers caused by predictive efficacy/toxicology?
It’s hard to know at the outset which approaches may be successful (Which drugs are toxic? Which therapies are going to be effective? Which drugs will be inexpensive?)
This uncertainty, and lack of predictive efficacy is a significant barrier to translation.
What kind of team is needed to progress from T0 to T4 most efficiently and effectively?
Several specialists
Multi-disciplinary teams with knowledge domains that are complementary and synergistic.
This team approach will be a paradigm shift in how we view and execute translational research
