In an average year, there’s nothing quite so contentious as talking about vaccines. Maybe it’s because they are safe and effective, maybe it’s because they’ve largely eliminated dozens of deadly diseases from our lives, or maybe it’s just because they are a medical intervention that we all get at some point — whatever the reason, vaccines are a very hot topic.
And 2020, for all its nightmarishness, is no different.
The promise of a vaccine during a pandemic is truly enormous. As someone who regularly writes about vaccination, it has been amazing to watch the media storm that accompanies every minor update in the progression of these new vaccines, going from a vague dream in a scientist’s brain to a reality being injected into people to prevent them from getting COVID-19.
But there’s a constant question popping up, that has become even more urgent with the news that one vaccine trial has been paused due to a serious adverse event in a participant: Are we rushing through the approval process? And perhaps more importantly, are COVID-19 vaccines going to be safe?
The short answer is yes, with an if. The long answer is that we can’t know anything for sure, but what we do know so far is quite reassuring.
Let me explain.
Approving a vaccine is a lengthy process. This makes perfect sense, because vaccines are by design the safest of all medical interventions — they have to be, because we give them to mostly healthy people. You can get away with the occasional problem with a drug that stops already very sick people from getting worse, but when the person having the intervention is perfectly healthy we have to go to great lengths to ensure that they won’t be harmed.
And we do. Massive trials, with 10,000s of participants, that take years to conduct.
The way this works is through a 4-phase process. The first two phases are pretty basic — giving the vaccine to a small number of people to make sure that, over the course of a month or two, they don’t all die and that their immune systems do react to the vaccine. After Phase 1 and 2 trials have been completed, you move on to Phase 3, which is the biggie. This is where scientists randomize very large numbers of people into two groups, one that gets the vaccine and another that gets the control. Phase 3 trials are where we find out if the immunization actually prevents the disease that it is meant to, and whether it causes any severe adverse events that are too rare to have been picked up in the small samples of earlier phases. Phase 4 is a post-marketing safety mechanism, that allows us to see if there are any really rare adverse events when the vaccine is given millions of times.
Now, there are already numerous vaccines for COVID-19 that have completed Phase 1 and 2, which isn’t really surprising. Phase 1 trials only require a dozen people or so, and Phase 2 trials are only a little bigger. While the time to conduct these has been compressed from years to months, it’s not overly worrying given that most of these trials are really only testing to make sure that most people who get the vaccine actually do have an immune response (and don’t immediately keel over when given it).
But people have raised concerns — legitimate ones — about rushing through the vaccine approval process, and particularly Phase 3 trials. These normally take years to conduct, because they require 1,000s of healthy volunteers to take an experimental vaccine, who are then followed up for long enough that we can be sure even the rarest issue caused by the vaccine isn’t going to be a problem. Recruitment is hard, retaining your study participants is hard, and making sure your study is robust enough that you can be sure the vaccine is safe is incredibly hard too. This is part of the reason that many vaccines fail at Phase 3, and why the average length of time for this phase is around 3 years.
Most governments are planning on rolling out COVID-19 vaccines early next year, giving us a timeline of 6–10 months for COVID-19 vaccine trials.
Is this a problem?
The most important phrase you can ever learn when reading about epidemiology is simple: it depends. If you had told me last year that a government was planning on mass vaccination based on early results from a Phase 3 study conducted over the course of 6 months, I’d have told you that it sounded quite worrying.
But this year, we have a pandemic on our hands, and things are a bit different. Take the Moderna vaccine trial, for example. This is a new COVID-19 vaccine that has performed very well in Phase 1 and 2 trials, and is currently being conducted in 100 locations across the globe. Millions of doses of the vaccine have already been sold to numerous governments.
Am I worried about this trial? Well, let’s look at the facts — it’s being conducted over the course of 24 months, has an excellent protocol, and is aiming to recruit thirty thousand participants. Even for a Phase 3 vaccine trial, that is a huge number, and having a read through the study protocol it seems like the research is being done in an impressively robust way.
“So why have concerns been raised?”, you ask. Well, despite the lengthy timeline of the study itself, many governments are planning to start rolling out the vaccine after just 6 months or so of evidence accumulation. In other words, when the vaccine comes out, it’s entirely possible that there are long-term issues that we simply do not know about yet. They probably won’t be common, and are unlikely to be severe, but we cannot exclude the possibility that they exist.
And this is where the whole “it depends” thing comes in. In a usual year, I’d say that the risk — low as it might be — of rare long-term side-effects from the vaccine was too big of a problem, and we need to wait until the Phase 3 trial is completed. But this isn’t a normal year. The health and social costs of COVID-19 are mounting day by day, but might largely go away if the vaccine is both safe and effective.
This is where we get to the troublesome calculus that comes with many public health decisions. At six months, we’ll know whether the vaccine prevents COVID-19, at least in the short term. If it does, is it worth trading the potential of a future problem for the immediate and substantial benefit of an effective immunization today?
Unfortunately, that’s a question that only individuals (and their governments) can answer. We’re all going to have to make our own minds up about whether the massive costs of COVID-19 outweigh the potential risks of a vaccine that is still being trialed. I can’t look into my crystal ball and tell you whether it will be a good idea for you.
What I can say is that, as an epidemiologist, if a COVID-19 vaccine gets through a shortened Phase 3 trial with no major issues, I will be first in line to get one. Yes, there are risks, but given the impressive and amazing scientific effort going into these trials, and the terrible damage that the disease itself is causing, I think the rewards are much more substantial. Of course, this does assume that the trial will find a safe and effective vaccination, which is definitely not a certainty at this point.
And on this point, I think that Astrazeneca pausing their Phase 3 vaccine trial because of a suspected adverse event is very reassuring. This is exactly what you want to see — the manufacturer is being careful to make sure that even a single event among thousands is thoroughly investigated, because they want the vaccine to be as safe as possible before it is released.
So no, you probably don’t need to worry about COVID-19 vaccines in development.
But, as with most things in epidemiology, it really does depend.