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The clinical development phase, divided into three stages, is where a vaccine candidate is tested on human participants. The National Institutes of Health, working with Moderna, has already initiated Phase I trials for an RNA vaccine, while many other candidates are still in various stages of development.
“This is unprecedented, we've never experienced such rapid development in any drug or vaccine before,” says John Cooke, a physician scientist at Houston Methodist Hospital who is currently collaborating with GeneOne Pharmaceuticals to develop an RNA vaccine for COVID-19.
“This is light speed, this has never been done before in the development of any drug or vaccine,” says John Cooke, a physician scientist at Houston Methodist Hospital who is currently collaborating with the pharmaceutical company GeneOne to develop an RNA vaccine for COVID-19.
...while the 12 to 18 month timeline is considered a guideline, many experts believe it is within reach, but it is not a guarantee.
Phase I: Determining appropriate dose levels and monitoring for adverse effects
During a Phase I trial, a vaccine or treatment is administered to healthy volunteers. The primary focus is not to assess the efficacy of the vaccine or treatment—that evaluation comes at a later stage.
In Phase I, researchers experiment with various doses to determine the vaccine's safety and ability to trigger an immune response. For COVID-19, most of the vaccines being developed aim to target the spike proteins present on the virus's outer surface.
“Individuals who have recovered from infection possess antibodies against the spike proteins, so it is logical to vaccinate people against that protein,” Cooke explains.
If a vaccine successfully completes a Phase I trial, it indicates that initial data supports its safety, allowing it to be tested on a larger group of volunteers.
Phase II: Evaluating therapeutic doses in individuals at high risk
After a Phase I trial establishes the ideal dose and confirms the vaccine's safety, the vaccine progresses to a Phase II trial. This stage is larger and involves volunteers receiving a therapeutic dose, the one considered effective for the general patient. Phase II trials typically involve individuals at higher risk for COVID-19, such as the elderly or those with pre-existing conditions. Healthy people working in high-risk settings, such as healthcare professionals, may participate in either Phase I or Phase II trials, depending on the situation.
If a vaccine successfully passes a Phase II trial, it means there is evidence supporting both its safety and effectiveness, paving the way for a larger-scale trial.
Phase III: Expanding testing to a broader population
By the time a vaccine has completed both Phase I and Phase II trials, researchers will have a clear understanding of the doses required to trigger an immune response, as well as the possible side effects. Phase III is where these findings are tested on a much larger scale.
“This is the conclusive trial,” Cooke remarks. “This will truly determine whether it is effective.”
Phase III trials also provide insight into the extent of a vaccine’s effectiveness. Like any drug or vaccine, individuals may react differently. Given that Phase III trials involve more participants, researchers can better understand how varied the responses might be within the general population.
“Individuals can have different reactions,” Cooke explains. “Some might produce antibodies to one part of the protein, others to a different part, and some will develop antibodies to both.”
If a vaccine successfully passes Phase III trials, it signifies that it has been proven safe and effective in a broad group of people, and is ready to move on to regulatory review, approval, manufacturing, and large-scale distribution. In other words, a vaccine that clears Phase III trials has a very high chance of being made available to the public, provided there are no unexpected issues with mass production.
Moving swiftly while maintaining safety and effectiveness
Developing and testing a COVID-19 vaccine comes with a natural tension due to the urgent need. On the one hand, a vaccine would significantly help mitigate the crisis. On the other, if it’s not thoroughly tested for both safety and effectiveness, it could lead to unforeseen side effects or even worse, create a false sense of security.
The fact that a Phase I trial has already begun, despite the virus being first identified in late 2019, highlights the severity of the threat posed by the coronavirus. That the process has progressed to this point is a historic milestone, reflecting the collaborative efforts of a global scientific community.
The current estimate for a COVID-19 vaccine suggests it could be available within 12 to 18 months. However, as coronavirus expert Peter Hotez shared in an interview with the Houston Chronicle, the current fastest development record is four years, set by the mumps vaccine. In the same interview, Hotez points out, “A lot of smart people are thinking in innovative ways about how we could do more things in parallel. But we have to also set some realistic expectations that we might not have that vaccine in a year or 18 months — and maybe not for two or three or four years.”
Therefore, the 12 to 18 month estimate is a guideline, one that many experts believe is achievable, but not a guarantee. However, given the urgent need, there are ways the FDA is willing to speed up the process.
“If the drug offers significant benefits for an unmet need, the FDA is open to accepting more risk,” Cooke explains. “They are working to adapt to the current situation.” The rapid pace of both the development and testing of potential vaccines is driven by the urgent need for an effective preventative treatment.
“We want to move as fast as possible while maintaining rigor,” Cooke states. “These goals are definitely in tension; moving quickly and adhering to rigorous standards are often at odds. But we make an effort. We’ll trim some corners we believe we can safely, fast-track certain processes where possible, but always with safety at the forefront.”
