Throughout the Covid-19 pandemic, there’s been one hope that we’ve all relied on. We’re all waiting, with bated breath, for the day that scientists announce a successful coronavirus vaccine, because then we can get a jab and go back to the humdrum existence we enjoyed in 2019.
And, according to Russia, that day is today. In the last 24 hours, Vladimir Putin has apparently approved the world’s first coronavirus vaccine. Big news indeed.
But a lot of people are understandably confused at this announcement. We’ve been told for months that the race to find a vaccine is more of a marathon than a sprint. Even the optimistic targets of the most advanced vaccine programs are only aiming to start delivering doses at the end of 2020. How is it that Russia has managed to score the ultimate coup and finish testing a vaccine months before anyone else?
It turns out, unfortunately, that they haven’t really. In actual fact, the only discernible difference between Russia’s vaccine and any of the others you’ve seen in the news is that this one has skipped most of the testing phases that come before licensing. We actually have no idea if it is safe and effective at all.
Let me explain. Vaccines – and most other medical interventions – are tested in four phases of human experiments. Phase one trials are very simple – give the vaccine to a small group of people at different doses to see which one is safe. Phase two trials go bigger, with a few hundred people, and usually compare the vaccine against a control to a) make sure that it is triggering an immune response and b) see if there are serious side-effects that the phase one trial missed. Phase three trials are the biggest pre-licensure studies, and they test whether the vaccine actually works – they randomly allocate people into two groups, vaccine versus control, and follow them over months to see if the people who received the vaccine get infected less than people who get the control. These trials are huge, with tens of thousands of participants, so they can also look for rare side-effects that the smaller studies cannot pick up. Phase four trials are post-licensure, and are there to check whether the vaccine causes any really rare issues, because you might not pick up something that happens one in 1,000,000 times until you vaccinate enough people.
Now, the key thing here is the phase three trial. Until these are completed, all you’ve shown is that the vaccine doesn’t do harm to everybody who takes it, and that there is some antibody response within a month of getting the immunisation. There are numerous examples of vaccines that looked promising at phase two – they caused antibody responses and were safe enough – that turned out to be useless at actually preventing disease. HIV vaccination has traditionally been incredibly difficult, with at least one vaccine that passed phase 2 trials with flying colours failing to actually prevent the disease. One vaccine for herpes looked promising but didn’t create a sustained immune response and so didn’t prevent actual herpes infections. Another immunisation for staph, a nasty disease that kills people in hospitals around the world, not only failed to prevent infections at phase three despite being perfect at stage two, but actually increased people’s risk of death.
This is why we do these studies. It’s not for fun, it’s because sometimes things that look really good early on turn out to be pretty useless.
Which brings us back to Russia. While phase one and two trials of the vaccine have been pre-registered, they are reportedly ongoing and have not yet posted any results. There is no evidence a phase three trial has even been started, never mind completed.
This leaves us with the obvious conclusion: no one really knows if this vaccine actually works. Phase one and two trials can inform this question, but because they only measure antibody titers or another surrogate outcome they can’t tell us whether the vaccine prevents the disease it’s meant to stop. By all accounts, people inoculated with the Russian vaccine do have antibodies, but these may not last, may not provide enough protection, or may fail for another reason because the immune system is fiendishly complex. We just don’t know.
What this means is that, in effect, anyone taking the vaccination will be part of a grand clinical trial, but without a solid control group. Now, I cannot speak for people in Russia, especially given they’re facing nearly one million cases of coronavirus, but I would not be keen to sign up to be a guinea pig to test a vaccine that has unknown efficacy and unknown levels of risk. Even worse is that, by all reports, the vaccine is moving to immediate mass manufacturing, which means the phase three and four trials may be skipped altogether, leaving us with no idea whether the vaccine is safe and effective at all.
Ultimately, I’d be a bit terrified of taking a vaccine that has rushed through the process of development. There are reasons – good ones – that we don’t just give everyone a vaccine when we reach phase two. Vaccines are, by definition, given mostly to healthy people, which means they have to pass the highest bars for safety of any medical intervention around. Even minor risks of severe issues are often unacceptable, which is why we do these enormous trials with tens of thousands of people.
Maybe the Russian vaccine is indeed effective. But maybe it only produces an immune response for two weeks, and the hundreds of millions of planned doses do nothing at all to prevent the pandemic. We simply don’t know and, given that it’s being rolled out within a month, perhaps we never will.
Gideon Meyerowitz-Katz is an epidemiologist working in chronic disease.