All those therapies once approved, are ready for translation into practice. That's the T3 stage, Clinical Implementation Research. The clinical implementation stage of translation involves adoption of interventions that have been demonstrated to be useful in a research environment into routine clinical care for the general population. These are the therapies that emerge into your doctor's office, that diagnostic tests that emerge to define and diagnose disease at much earlier stages. Everything from pregnancy testing to genetic testing to looking at who responds to vaccinations, to new drugs, new therapies for a whole spectrum of diseases, new diagnostic measures, imaging, and medical devices like pacemakers and other diagnostic devices, surgical devices for new operations. All of those are included in Clinical Implementation Research. Now, this stage involves several new types of investigations. Those can include evaluating the results of the clinical trials. Clinical trials are very focused and narrow investigations under highly controlled situations. You can think of T3 The Stage of Clinical Implementation Research into looking at how those therapies perform when applied to the general population who can benefit from them. Also, new clinical questions and gaps in care can arise, things that were not found in earlier T2 clinical trials can emerge. Implementation research also might involve, how best to deliver this care, refining who those therapies apply to, helping clinicians decide on standards for diagnosis and delivery of treatment. All of these, sets the stage for thinking much bigger, public health implementation, the T4 stage. The T4 stage is about translating these therapies into the health of the general public of communities, of states, nations, and the world. At this stage of translational research, researchers study health outcomes at the population level. We may have a great therapy for heart disease, but does it help the whole population or just a segment of the population? Does that therapy work in different areas of the world with different constraints? How do we measure at a population level, the effect of those therapies? And how can we use those diagnostic methods to prevent and diagnose illnesses so that we can treat them? These findings also help guide scientists working to assess the effects of current interventions and to loop back and develop new ones. So while we think of the T0 - T4 spectrum as a straight arrow progressing from one to the other, each stage feeds back on the previous stages and it works to translate basic discoveries, all the way up to population health implementation and improvement. And at each stage, we gain insights that can be applied forwards and backwards. Organizes all of this. In the United States, that organizer is the National Institutes of Health. The National Institutes of Health is the overriding Institute for Medical Research in the United States and provides funding and guidance and oversight in a whole spectrum of disease states. There's the National Cancer Institute, the National Eye Institute, the National Institute for Aging, the National Institute for dental and craniofacial research, the National Institute for General Medical Science, the National Institute for Medical Health and the National Center for Advancing Translational Science. The only Institute at the National Institutes of Health with a verb in its name, advancing. Let's talk a little bit about NCATS, the National Center for Advancing Translational Sciences. NCATS is an organization like any other organization. There is a director who oversees a variety of functions of the National Center for Advancing Translational Research. There's an office of grants management and scientific review. So, studies and centers that are funded by NCATS, go through a review process where scientists and organizations submit proposals for studies they would like to sponsor and research that they would like to do. Now, many of these studies are organized by NCATS and are used to direct and address national priorities for translational research. For example, there's the Office of Rare Diseases Research. The Office of Rare Diseases Research deals with rare diseases and what are called orphan therapies. Therapies that might not otherwise be developed without an intervention. There's the Office of Policy Communications and Education. And that office is responsible for developing educational material to advance the capabilities of the National Translational Science Research workforce. There's an Office of Strategic Alliances which builds bridges between the foundation and industry. There's the Division of Pre-clinical Innovation which looks at innovations that could be moved from that the T1 - T2 stage. There's the Division of Clinical Innovation that looks at moving innovations from T2 - T3. And of course, like any organization, there's an Office of Administrative Management. There are a variety of subprograms and initiatives that are sponsored by NCATS and these are all organized around clinical and translational science. Among the programs which I haven't mentioned, there are some really cool stuff. So for example, tissue chip testing for drug screening. So, of course, we can't screen promising drugs for rare diseases and any diseases that require treatment of cells in people right away. We want to make sure that they're effective and safe and we want to understand what they do to the cells. So scientists have invented tissue on a chip. These are tiny microchips that are bioengineered to improve the process of predicting whether drugs will be safe or toxic in humans. They can be coated with cells, they can be coated with cells from different tissues or proteins from different tissues, and they can measure across a variety of tissues in this incredibly tiny device. How those drugs affect processes that we're interested in treating? There's also a Clinical and Translational Science Awards program. This is a major program that funds scientific hubs, CTSA, Clinical and Translational Science Awards at over 60 institutions across the country. And this is the translational research highway that moves discoveries from T0 all the way up to T4. This structure was developed specifically for this purpose.