Mike Frick, Treatment Action Group

So what are clinical trials? Clinical trials are studies that are done involving real humans, who we refer to as participants because they are participating in a research study and have agreed to do so. In early clinical trials, the participants tend to be people who are referred to as healthy volunteers. Basically what that means is that they're people without tuberculosis and they're volunteering to participate in early stages of research to collect basic information on the safety of what's being studied before that's tested in people who have the disease TB in later stages of clinical testing.

Clinical trials are the main way that researchers find out if a new drug or treatment regimen, vaccine or diagnostic is safe and effective in people. Clinical trials are broken into different phases, usually referred to as phase one, phase two, phase three, sometimes phase four. And we'll go into more detail on the phases of clinical trials in later modules.

If clinical trials show that a new tool is safe and effective, then it may be evaluated for approval by national regulatory authorities. These national regulatory authorities, which we sometimes refer to with the acronym NRAs, are basically government agencies that are responsible for overseeing the conduct of clinical research and for evaluating the outcomes of that research. They're the ones who are judging all of the data and evidence from clinical research, supporting the use of a new tool to see if it's ready to be used in routine care and introduced into a health system.

Common regulatory bodies that we hear a lot in TB would include the Food and Drug Administration or the FDA in the United States, the European Medicines Agency, or EMA for the European Union, or SAHPRA, the South African Health Products Regulatory Agency in South Africa. Almost every country has a national regulatory body responsible for governing research in that country and evaluating new tools for approval and the interaction of these bodies with each other. And with the evidence coming out of clinical research is what makes the approval process.

So what is operational research? Operational research, sometimes also called implementation science or operations research, is any research conducted to help us understand how to use new TB tools most effectively or most efficiently within a health facility or a health system. Ensuring access to new TB tools relies on being able to conduct operational research. And that's because operational research helps to find challenges and solutions to introducing new tools and to expanding their use to all people who need them.

Clinical research is vital for the approval of new tools, but not every question we have about how to use a new tool can be answered in clinical research. And so a period of operational research or implementation science following the approval of a new tool is really critical for expanding access to that technology.

So for example, after India's national TB program introduced a diagnostic test called TrueNat MTB/RIF, researchers used operational research to test how feasible it was for health workers to use the test and what impact it had on their ability to diagnose TB. They found that the tests significantly increased the number of people with TB who were diagnosed. They also found that the average lab technician responsible for running the test became comfortable using the new test platform after performing it for about 10 times, which is a pretty fast rate of learning how to do something new. So operational research like this can provide advocates with information that they can use to educate their governments about the potential impact of new diagnostics and advocate for greater access to tools like TrueNat MTB/RIF.

This information is really applied, it's hands-on, it's about the actual lived experience that people with or at risk of TB seeking care and the extent to which new tools are meeting their needs and where those needs are not being met. We learn from operational research what needs to be done to bridge that gap, and to improve practice and quality of standards.