On August 11th, Vladimir Putin announced Russian health agencies had approved the world’s first vaccine for widespread use against COVID-19: Sputnik V. Yes, that’s really what they decided to call it. And it’s potentially really good news but, many experts are skeptical as to whether the vaccine works because it’s been tested in a wired way. The vaccines are technically drugs and get approved by regulatory drug agencies. They are supposed to publicly prove themselves in a very specific set of scientific tests. This is, in large part, why vaccines as a whole are so safe and effective. But this is not what happened with this Russian vaccine. Its developers haven’t published any of the results from human tests but they claimed success even before starting the kind of testing you need to see if a vaccine works. Alright, so, to back up: drug trials in humans, also known as clinical trials, are typically organized into four to five stages, or phases. These can sometimes be combined, but they’re usually discrete because each builds on the previous ones. In the US, they are creatively named phases 0, I, II, III, and IV. But phase IV happens after the drug hits the market, so they will be focusing on phases 0 through III here.
Phases 0 and I are generally short, small studies intended to establish that the drug does the very basics of what it’s supposed to do, and doesn’t cause tons of harm in the process. Since these trials are usually the first time a drug has been given to people, researchers are watching out for negative side effects, or, in trial lingo: Adverse events. They also generally try to figure out what does would be best. For instance, a Chinese company called CanSino began a phase I trial for its COVID-19 vaccine on match 16th. They gave 108 participants a low, medium, or high dose of the vaccine. And while quite a few of those people bad mild to moderate side effects like fatigue and headaches, the vaccine appeared safe enough to use in people. So, it moved to Phase II. Here, the scientist continues to look for adverse events and evaluate dosing. And the question of whether the drug does anything becomes more prominent. Participants’ numbers also typically go up. Like, CanSino’s phase II tested two different doses against a placebo in about 500 people and, as hoped, vaccinated participants started producing antibodies that can neutralize the virus, and had others promising immune responses as well. Now, at this point, you might be wondering how Sputnik V fared in its Phase I and II trials. And so is everyone. Although two combined Phase I and Ii trials for it are listed online as ‘ Complete’, their results haven’t been published. So, everything we know comes from the Russian government and the researchers involved. There’s no public data about how the vaccine works, or how well those trials went. But more to the point: even if they did go well, the positive phase II results don’t guarantee the vaccine works in the real world.
While things like antibody levels are associated with protection in animals, immune reactions are complicated. And Phase II trials don’t test whether a vaccine prevents people from getting sick. That doesn’t happen until Phase III. These trials are typically hundreds, thousands, or even tens of thousands of participants larger. That’s in part because researchers want to see if or how many people catch the disease after getting the vaccine. So, they need lots of people, to make sure that a good number of them are exposed to the virus in their daily lives. And that can take a long time, which is why Phase III trials usually take a year or years, start to finish. Another reason for the big numbers at this Phase is to spot rare and serious adverse events. Even something that happens once in every ten thousand vaccinations can be a big deal, since we may want to vaccinate hundreds of millions of people. And these also can take some time to manifest. So phase III trials are really important, both as measures of how well a vaccine works and how safe it is, and their large numbers and longer time table are key to all of that. Now, when Putin made the announcement, it wasn’t clear if Russia was planning to start one of these trials. Since then, other sources have said that the vaccine’s approval is actually dependant on positive Phase III results and that those trials have started, or will start soon? In several countries; the details are still fuzzy. Even if that’s the case, though, government officials have also said that they want to start administering this vaccine in October, which wouldn’t give those trials time to show anything. That’s why doctors and public health experts are so unnerved by how this is all playing out.
Now, Russia isn’t the only one taking risks or skipping steps in hopes of delivering a vaccine as soon as possible. Like, in the US, a company called Moderna launched into Phase I and II trials for their COVID-19 vaccine before completing pre-clinical trials in animals. Then, they went into Phase III before finishing Phase II or publishing the full results from Phase I. Also, the pharmaceutical company Pfizer announced that they may apply for FDA approval for their vaccine candidate in October, even though it’ll still be in Phase II and III trials. And while it would be unprecedented for the FDA to grant them that approval, this week, the FDA commissioner said the agency might consider an emergency use authorization, if a company submitted compelling paperwork before the end of clinical trials. Which is another way, isn’t that unusual. We have emergency authorization for other COVID-19 therapeutics in America. And China has implemented its version of emergency vaccine authorization for its military and at-risk citizens, even though their vaccine is still in clinical trials.
But that’s not what Russia is initially said they were doing, and it’s still not entirely clear whats going on. They seem to be all in on this as yet unproven vaccine. And that’s a pretty risky bet, considering that more than a third of drugs hat down well in Phase I and II fail in Phase III. It’s possible, of course, that the gamble will pay off. Sputnik V could be a safe and effective vaccine. But, if the vaccine doesn’t work, or worse proves truly harmful, it could hurt a lot of people, undermine control efforts, and ruin everyone’s trust in whatever vaccine or vaccines succeed it. It would be amazing if this vaccine pans out. But over the years, we have developed a very specific and rigorous method to make sure any drug or vaccine is as effective and safe as possible. This one isn’t following it. All this uncertainty surrounding, like, everything to with this pandemic is hard. So at this point, all we can do is to wait and see.