How Do Clinical Trials Work?
With all the talk about the development of a potential COVID-19 vaccine, and the news that clinical trials of some candidates have already begun, you might be asking yourself how clinical trials actually work. Any vaccine approved for use on millions of Americans must go through a rigorous testing process, including research phase, preclinical phase, clinical development, regulatory review and approval, manufacturing and quality control – so it’s important to remember that just the fact that testing does not mean, that a vaccine is inevitable.
The clinical development stage, which is divided into three phases, is when a potential vaccine is tested in human volunteers. The National Institutes of Health, in collaboration with pharmaceutical company Moderna, has already begun Phase I trials of an RNA vaccine , while many more candidates are still in development .
“This is the speed of light, something that has never been done before in the development of any drug or vaccine,” says John Cook , a medical scientist at Houston Methodist Hospital who is currently working with the pharmaceutical company GeneOne to develop an RNA vaccine against COVID. 19 .
Phase I: Checking dose ranges, looking for side effects
A Phase I trial involves the administration of a vaccine or treatment to healthy volunteers. The main purpose is not to test how effective a vaccine or treatment is; it will come later.
In Phase I, researchers test the dose range and examine whether the vaccine is safe and whether it induces an immune response. As for COVID-19, most vaccines under development target the spike proteins found in the outer envelope of the virus.
“People who survived the infection have antibodies against the spike proteins, so it makes sense to vaccinate people against this protein,” says Cook.
If a vaccine passes a Phase I trial, that means preliminary evidence suggests it is safe and can be tested in more volunteers.
Phase II: Testing therapeutic doses in at-risk individuals.
Once the optimal dose has been established in the Phase I trial and the vaccine has been determined to be safe, the vaccine proceeds to the Phase II trial. The Phase II trial is larger and includes volunteers who are administered a therapeutic dose that is the effective dose for the average patient. At this stage, the volunteers will be people at high risk of COVID-19, such as the elderly or people with underlying medical conditions. Healthy people working in high-risk settings, such as healthcare professionals, may be included in Phase I or Phase II trials, as appropriate.
If a vaccine passes a Phase II trial, it means there is evidence that it is safe and effective, and a larger trial could be done for that.
Phase III: testing at a larger scale
By the time the vaccine has passed the Phase I and Phase II trials, researchers already have a good idea of what doses are needed to elicit an immune response, as well as any potential side effects. Phase III is when all of this is being tested on a larger scale.
“This is the ultimate test,” says Cook. “This will allow you to really determine how effective it is.”
A phase III trial is also where researchers gain insight into the range of effectiveness of a vaccine. As with any medicine or vaccine, some people respond better than others. As the Phase III study is larger, it will give researchers a better understanding of how variable the response can be in the general population.
“People react differently,” says Cook. “Some people develop antibodies to one part of the protein, others develop antibodies to another part of the protein, and some people develop antibodies to both.”
Once a vaccine passes a Phase III trial, it means it has been found to be safe and effective in a large group of people and can move on to regulatory review and approval, production, and large-scale distribution. In other words, if a vaccine passes Phase III trials, there is a very good chance it will be offered to the general public, barring any unforeseen problems when it comes to large-scale production.
Move quickly while ensuring safety and efficiency
Given the urgent need, the development and testing of a COVID-19 vaccine is fraught with inherent stress. On the one hand, a vaccine will go a long way in mitigating this crisis. On the other hand, if a vaccine is not fully tested for safety and efficacy, it can cause unintended side effects or even cause disaster, giving people a false sense of security.
The fact that the Phase I trial has already begun, despite the virus being first detected at the end of 2019, speaks to the severity of the threat posed by the coronavirus. The fact that the process has already reached this phase is a historic achievement in which the efforts of the global community of scientists have participated.
The current estimate is that the COVID-19 vaccine will be available in 12-18 months. However, as coronavirus expert Peter Hotez pointed out in an interview with the Houston Chronicle , the current record from start to finish is four years for the mumps vaccine. In the same interview, Hotez notes that “many smart people think innovatively about how we could do more things in parallel. But we also need to set some realistic expectations that we might not have this vaccine in a year or 18 months, or maybe in two, three or four years. ”
Thus, an estimate of 12 to 18 months is a benchmark that many experts consider achievable, but not a guarantee. But given the urgent need, there are ways the FDA is prepared to expedite this process.
“If a drug offers tremendous benefits to an unmet need, then the FDA is willing to take a greater risk,” Cook says. “They’re trying to adjust to the situation.” The speed of development and testing of potential vaccines is driven by the very urgent need for a viable preventive treatment.
“We want to act as quickly and strictly as possible,” says Cook. “This is definitely a conflict; moving quickly and doing something strictly are almost opposites. But we are trying. We will cut some corners that we think we can cut, speed up some processes that we think we can speed up, but we do not forget about safety. “