As the coronavirus disease 2019 (COVID-19) continues to wreak havoc in communities across the globe, researchers are racing to find successful treatments for the deadly virus and ideally, a vaccine against COVID-19. While it is understandable that everyone wants a miracle cure as soon as possible, it’s not that easy.
All new medical drugs and treatments have to be thoroughly tested in clinical trials before they are licensed and available for patients. This takes time, planning and extensive oversight.
So just what is a clinical trial and what are the steps researchers take to bring a drug from the lab to your local pharmacy? To learn more, we talked to John Buse, MD, PhD, executive associate dean for clinical research at UNC School of Medicine.
Clinical Trials Defined
Nearly every medicine we take and vaccine we receive began as a clinical trial, which is when researchers study a treatment given to people to determine how safe and effective it is.
Clinical trial researchers can study many things, including:
- New drugs not yet approved by the Food and Drug Administration (FDA);
- New uses of drugs already approved by the FDA;
- New ways to give drugs, such as in pill form instead of through an IV;
- New tests to find and track disease; and
- Devices that monitor or relieve symptoms of a disease.
“There are different ways to eventually having a drug we can prescribe,” Dr. Buse says. “The dominant one these days are targeted development programs.”
A targeted drug development program begins with an understanding of the basic biology of how a particular cell in your body works and then learning how that cell is important in a disease state. For example, understanding how a kidney cell might turn into a kidney cancer.
“Once you understand how the kidney cell works normally, you can look to see how it acts in disease states—what things are different?” Dr. Buse says. “And when you identify things that are different—if they look like they could potentially be leveraged to create a treatment—there is a process you can use to predict what that molecule you’re trying to tweak looks like inside the cell or on the surface of the cell.”
Then, researchers use computer modeling and a vast database of chemicals to determine how a particular chemical might interact with that molecule.
“It’s a matter of setting up a process where you can very quickly look for the interaction of a chemical with that molecule that you isolated from the cell,” Dr. Buse says. “And you can look for particular effects of that chemical in a test tube.”
If a treatment seems to work in a lab, the next step is to try the treatment in a mouse. “For example, does this treatment on a mouse with kidney cancer make the kidney cancer better,” Dr. Buse says.
If that answer is yes, the next step is to try it on another animal species such as a rat or a pig and then a non-human primate.
If the treatment is effective in these different animal species, the next step is to conduct human trials, which usually have four phases.
Phase I Clinical Trials
Phase I of a clinical trial is the first time the proposed treatment or drug is explored in humans. These studies are usually focused on determining the correct dose and side effects for the drug or treatment.
Dr. Buse says the phase I trial is designed to answer questions such as, “Do we need to use a little, or do we have to use a lot? Can it be dosed once a day or does it have to be more than once a day? Can it be given with food, or does it need to be on an empty stomach?”
Phase I trials usually only involve a small number of people (about 20 to 80) for a period of days to weeks.
Phase II Clinical Trials
Phase II trials focus on the safety of the proposed treatment and usually involve a larger group of people (100 to 300) over periods of weeks to months.
Phase II also begins to explore the efficacy of a drug. For example, “does it change the course of kidney cancer?”
Phase III Clinical Trials
Phase III trials compare the new drug or treatment to placebo (dummy tablets without active ingredients) or other available treatments. This phase of study establishes the benefit or efficacy of the new drug and provides more evidence of safety, as well.
“After phase III the FDA decides if this package of studies, going all the way back to the studies of chemicals in the lab in test tubes, through the animal studies and the human trials, suggests that the new drug is a safe and effective medication. And if yes, they get FDA approval,” Dr. Buse says.
Phase III trials have much larger numbers of participants (generally in the thousands) and can last several years. If a phase III trial is successful, a pharmaceutical company can request FDA approval to market the drug or treatment.
Phase IV Clinical Trials
Sometimes a drug or treatment may go through a fourth phase, which explores how well the drug works when it’s more widely used.
This phase occurs after a treatment has been approved by the FDA and is made available to the public. If problems occur, researchers will recommend restrictions be placed on the drug or recommend the drug be taken off the market.
Clinical Trials Take Time
Normally, clinical trials can take years to secure approvals and study results. However, the FDA has created a special emergency program for possible COVID-19 therapies called the Coronavirus Treatment Acceleration Program (CTAP). Dr. Buse says because there are so many patients, it’s possible to do these clinical trials faster.
“The only good news about COVID-19 is that the disease is severe enough and common enough that we have the capability to do a lot of treatment trials very quickly,” Dr. Buse says. “It’s not like doing a trial for skin cancer where someone will have a skin cancer, and you give them a medication and then you have to wait months or years to find out what the outcome is for that patient.”
With COVID-19, usually it only takes a few weeks to find out whether a patient will get better or they won’t, he says.
According to ClinicalTrials.gov, there are 2,654 studies currently registered that investigate the COVID-19. Dr. Buse is confident better treatments are on the horizon.
“We’ll find better treatments for COVID. I’m sure of that,” Dr. Buse says. “I do think we will also learn from COVID-times how to do studies faster and better for everyday ailments from balding to (more serious ones such as) diabetes to cancers. And what we need is for patients to seek out opportunities to participate in clinical trials so that we can continue to develop new and better treatments.”