Pharmaceutical company Moderna began the last and longest step in the process of testing its COVID-19 vaccine candidate at the end of July – a Phase 3 clinical trial. It’s a huge undertaking: their goal is to recruit 30,000 people, inject some of them with an experimental vaccine, and then follow each one to see how many of them get the coronavirus and how many don’t. It will take months, even with the federal government’s Operation Warp Speed compressing the timeline whenever possible. These months can seem endless as more than a thousand people die from COVID-19 every day in the United States.
The process is long and intensive for a reason, however. Just because a vaccine exists doesn’t mean it’s reasonable or ethical to just give it to people before there’s proof that it works, and sticking to the process is the reason. which vaccines on the market today are so safe.
“It is just fundamentally wrong to think that because of an emergency we should somehow reject certain aspects of scientific research,” says Alex John London, director of the Center for Ethics and Policy at Carnegie Mellon University. .
Researchers already know a lot about some of the vaccine candidates. Moderna’s vaccine, for example, has undergone phase 1 and phase 2 clinical trials, and it has been tested in monkeys. The tests did not raise any major red flags, and they showed that people injected with the vaccine produced antibodies against the coronavirus. But none of them have tried to answer the question people want to know the answer to: Can this vaccine prevent people from contracting COVID-19 in the real world?
To answer this question, the researchers are turning to a phase 3 trial. They will assay thousands of people with the vaccine candidate and thousands more with a placebo vaccine. Then they will see if fewer people in the vaccinated group receive COVID-19 than in the placebo group. They also monitor side effects.
The amount of data we currently have on COVID-19 vaccines is only a fraction of what scientists need before recommending anything be released widely. “The evidence that would convince me to get vaccinated against COVID-19 or recommend that my loved ones get vaccinated does not yet exist,” Natalie Dean, assistant professor of biostatistics at the University of Florida, wrote in a New York Times editorial.
If a vaccine is a car, phase 1 and phase 2 trials take place while it is still in the factory. In these trials, scientists are always trying to put together a vaccine that might work – they determine what parts they might need and how they should be used. If this assembly process goes well, the vaccine candidate can move on to phase 3, where they are taken for a heavily supervised ride on test tracks and into the real world. “Phases 1 and 2 allow you to say, ‘We have a lot to clarify and decide,’” says London. “Phase 3 says, ‘Alright, let’s test that now. “”
These real world tests often fail. Only a small percentage of pharmaceuticals – even those that look promising in preliminary trials – make it to Phase 3 and end up being approved for use. The success rate of vaccines is higher than that of treatments, but many of the successes of vaccines involve viruses that scientists are already familiar with. New viruses, like the novel coronavirus, are much more difficult to develop vaccines and have less chance of success.
9. Consider this brand new analysis by Lo and his colleagues: https://t.co/CV6FKoqKYb. Look at their data breakdown. Green Strengths represent industry leveraging existing knowledge. But the yellow paths are more difficult to crack. pic.twitter.com/nh8OcdloOO
– Alex John London (@AlexJohnLondon) August 3, 2020
Sticking to the car metaphor, once a vaccine hits the test track there’s a chance it will stop working (doesn’t actually protect people from COVID-19) or , in the worst case, crashes (has serious side effects). Its first test drives need to be watched carefully, so the people who design it can monitor exactly what is happening.
If, as phase 3 trials progress, scientists are starting to see clear signs is While working, they would stop the trial early and start working to get it approved by the Food and Drug Administration. “If what we’re testing really shows it works, scientists would be remiss to continue testing it on people,” says Karen Maschke, who studies human research ethics at the Hastings Center in New York City. But this is a rare exception to the rule. In almost all cases, you should complete a trial, she says.
It is especially important to take the vaccines throughout the process, as they are intended for people who are already healthy. If someone is already sick, the benefits of trying a treatment (even if it’s not clear how it actually works) could be worth the potential risks. It is much more ethically difficult to justify something that is still experimental for a healthy person. “A vaccine is the kind of thing we’re going to give to hundreds of millions of healthy people, or maybe even this vaccine could be given to a billion people,” says London. “We need to know it’s safe.”
Even if it doesn’t cause side effects, it’s risky to give people an experimental vaccine outside of a clinical trial and before researchers know if it actually works. People who receive an untested vaccine may feel safer and stop taking so many precautions (like wearing masks or avoiding indoor gatherings) against COVID-19, London says. This could increase the spread of the disease if the vaccine does not work. “We need to know if it works because people are going to change their behavior after they get it,” says London.
Releasing a vaccine to the public before it is proven safe and effective could also undermine public confidence in vaccines. “When it comes to science and anti-scientific sentiment, you have to be really, really careful to get enough data,” Maschke says. Researchers should be able to indicate the number of people in whom they have tested the vaccine and their statistical analysis to justify a recommendation. “Confidence in the process of developing new drugs and new drugs is fragile,” says London. “We cannot jeopardize it.”
There isn’t usually such focused attention on the clinical trial process, says London. “The public has a window into a discussion that they are usually not a part of,” he says. This process can be confusing, even at the best of times. Press releases, sound bites, and jargon can create the illusion that scientists know more about vaccine candidates than they do, or that they sound more promising than they actually are. For example, when experts say a vaccine worked well in a Phase 1 trial, they mean they didn’t see anything that would prevent it from moving to the next step in the process.
“It doesn’t mean the things the public cares about – is it safe; if I take this, does that mean I will not have any adverse events a year later; and will it protect me if I am exposed to the coronavirus, ”he says.
Answering these questions is possible, but it will take time. Going to chain speed can save some time, but solid and conclusive answers are worth the wait.