Mike Frick, Treatment Action Group

In this lesson, we're going to learn the basic steps in how new TB tools are developed, who's involved in developing new tools, and how this research and work is funded.

Developing new TB tools requires a rigorous scientific research process. Often this process is quite long and it always involves many different kinds of people and stakeholders.

This process looks different for diagnostics, medicines and vaccines, because these are different kinds of tools that require particular studies and methodologies. But in all cases, research activities for new TB tools have to be carried out so that they meet strict standards for safety, ethics, and scientific rigor.

It's important to be familiar with key concepts used to describe different types and phases of research in order to stay up to date with new TB tools as they are being developed.

The stages of research can generally be broken down as follows:

There's discovery, preclinical research, clinical research, approval of the new tool and its evaluation for that approval, post-market surveillance, which is what happens after the new tool has been approved and is on the market and available for routine use, and then operational research, which is sometimes called implementation science.

Diagnostic research follows a somewhat different approach than taken with medicines or vaccines. And in the case of diagnostics research, discovery research informs phases of research that are called evaluation, demonstration and implementation.

We will go into these processes in more detail in the modules on new medicines, diagnostics and vaccines; and your course guide includes links to videos that you can watch to learn more about the process for developing these technologies.

Understanding the research process will help you stay informed about what's happening in TB research and development.

The first concept you should know is called basic science research. Basic science research forms the foundation of knowledge that all the other stages of research rely on to make progress.

Basically, in basic science research scientists aren't trying to develop any particular new tool or technology yet. They're not trying to necessarily develop anything tangible at all. They're pursuing knowledge, basic information about something. The only product of basic science research is that knowledge which can then be used in the other stages of research and development. The knowledge gained during basic science research can lead scientists to think of ways that they can apply that knowledge in subsequent phases of research and development.

Discovery is the earliest phase of applied research. In discovery, scientists are looking for a protein in the body or in the TB bacteria that plays a role in the disease. They're studying what we call host pathogen interaction - how the TB bacterium interacts with the human immune system, how the immune system responds, how the bacteria responds, and that dynamic interaction. And they're looking at that interaction for clues about how they can target TB or train the immune system to respond to the disease. They may be looking for a molecule that they think could be used to treat TB or some aspect of the immune response that can be harnessed to design a new TB vaccine.

In discovery researchers are looking for what we call candidates, which are potential new tools that can be investigated in depth to see if they would make for a suitable new TB tool on their own or in combination with other candidates or pieces of information.

When such a candidate is found, it will first be studied in preclinical research. Preclinical research is typically done using what we call animal models or human cells or human tissues in a lab. So this isn't research in actual living people, it's research and animal model substitutes.

A lot of TB preclinical research is done in mice, in rabbits, in non-human primates like macaques. And a lot of it is done in human cells, not involving a live animal model at all, or tissue systems that can be studied in a lab under well-controlled conditions.

Like other phases of research, there are very strict standards for safety and ethics that have to be legally followed when conducting preclinical research.

Whenever you see that a new tool is in preclinical testing, the important thing to know is that this is when researchers are working to see if the candidate has the intended effect and appears safe when tested in animals or in human cells or tissue samples. It's that demonstration of safety preclinically, that would be necessary to take something into the clinic where it would be tested in humans. We're also trying to see at this stage, if it's promising enough to move forward.

Not everything safe in preclinical testing is worth trying in humans. So we're also making decisions about the scientific merit of different candidates that we're studying in preclinical development. If that preclinical testing provides enough evidence to suggest that the candidate is safe and effective for use in humans, and if funding is made available, then the process goes to clinical
testing and to clinical trials.