IRA FLATOW: This is Science Friday. I’m Ira Flatow. As the pandemic continues to set new records and stress overburdened hospital systems, one piece of hopeful news surfaced this week. Pfizer, in partnership with a German company BioNTech had an announcement that sounded almost too good to be true. It said their data, so far, indicate that their vaccine, which uses a new technique called mRNA, has an efficacy rate of 90%. That means out of 10 people who take it, nine will be protected from symptoms of COVID-19.

But as is often the case, drug company news announcements don’t necessarily paint the whole picture. And as other vaccine makers race to gather this same data, there’s still remains much to understand about how effective any approved vaccines might be, and how many lives they might save. So here to help fact check our vaccine news are my guests, Dr. Angela Rasmussen, associate research scientist at Columbia’s Mailman School of Public Health. Welcome back, Angela.

ANGELA RASMUSSEN: Thanks, Ira. Thanks for having me.

IRA FLATOW: And Dr. Natalie Dean, assistant professor of biostatistics, University of Florida. Welcome, Natalie.

NATALIE DEAN: Hi. Thanks, Ira. Thanks for having me.

IRA FLATOW: Dr. Dean, let me begin with you, with the claim Pfizer made on Monday. What is 90% efficacy, and how did they get to that number from their current clinical trial setup?

NATALIE DEAN: Vaccine trials, these Phase 3 efficacy trials, involve tens of thousands of participants. But we expect relatively few of them to ever be exposed to infection and to develop disease. And so what the trial has done– so it’s run for a few months, and 94 individuals have gotten sick with COVID-19. So they have symptoms, and they’re laboratory confirmed by PCR. And what we do is we look at how those cases split across the vaccine and placebo arm. And there are 90% fewer cases in the vaccine arm than the placebo arm. And that’s how we estimate efficacy and see that the vaccine is protecting.

IRA FLATOW: Now, I understand that the FDA was prepared to authorize a vaccine with as low as 50% efficacy. 90% feels like an extremely nice surprise.

NATALIE DEAN: It’s exciting. We really didn’t know how efficacious these vaccines were going to be. It’s a new virus. It’s new vaccines. And 50% was set as a lower bound, sort of when a vaccine starts to be worthwhile enough to have that public health impact. And we really didn’t know what to expect. So this is exciting, and it probably bodes well for other vaccines, targeting the same virus, as well.

IRA FLATOW: Can we tell if this is correct, based on what they’ve told us?

NATALIE DEAN: There are a lot of details missing, of course. What we do have is the protocol. So that had been published in advance, and we know some details about the trial population. And so we know what the primary endpoint they’re looking at, the symptomatic disease, how it’s defined. We know their analysis plan. And those things are quite rigorous and robust. The things that we don’t know– we don’t know how these cases are splitting across the trial population. We don’t know if they’re primarily in the younger population. It’s possible.

You could imagine that all of the older adults who are participating in the trial, maybe they were all staying home, and so none of them got infected or exposed. And in that case, we wouldn’t really know how well the vaccine works in that population. So we still want to see some of that subgroup data. We also want to see how well the vaccine is preventing severe disease. We want to see the data on infection, so that’s distinguished from symptomatic disease. So there’s still a lot of details out there. But the top line number is very encouraging.

IRA FLATOW: As I noted before, this is an interim data analysis. Pfizer has to get, I understand, another 70 or so symptomatic cases among their participants before they can conclude this trial. How much of this good news is likely to change between now and that final analysis?

NATALIE DEAN: In trials, we have this concept of the interim analysis, where we can take early looks at the data. And if something is working really well, we can have sufficient data to demonstrate that before the trial concludes. So the evidence that they are likely to have so far, based on what we’ve seen, is very strong, and would be sufficient to totally stop the trial if they wanted to. But they’re continuing because they want to accrue more information, this subgroup data and more data on severe cases.

One question we’re interested in is how durable is the vaccine effect. So these people were only vaccinated relatively recently, a few months ago. And so one thing we want to see is, does that effect persist over time? And so it is possible that that effect could wane, and that would reduce the final efficacy estimate at the end of the trial.

IRA FLATOW: That brings me to the next question I was going to ask. Is efficacy the same thing as effective?

NATALIE DEAN: We have different names for these concepts. So efficacy refers to the idealized biological fact. It’s when all of the conditions are correct, and this is what we have from a well-controlled clinical trial, where everyone’s receiving the doses per protocol at the correct timing, the cold chain has been maintained.

So efficacy, we can think of as our idealized, our upper limit when everything’s working perfectly. Effectiveness is what happens when we actually go out into the real world, and things may not be quite as perfect. And so we can see the effectiveness tend to decrease a little bit, relative to that idealized estimate.

IRA FLATOW: Angela, let me bring you into this real world picture, as we keep hearing any vaccine is still months away from being available to you or to me. What are the types of conditions that you see affecting how many people can access this vaccine– I’m talking about the Pfizer one– and how well it works for them.

ANGELA RASMUSSEN: Well, as Dr. Dean said, there are many challenges to distributing this vaccine. This vaccine is also a two-dose regimen. Secretary Alex Azar said that by the end of the year, there should be $20 million doses of the Pfizer vaccine available. In practice, that means that there’s only actually 10 million doses, because people, in order to be protected with this vaccine, have to receive two shots 21 days apart. And then they really aren’t considered to develop full immunity until a week after that.

So there will be a limited number of doses available initially. That should expand, but there is going to be a real challenge in distributing this vaccine in the real world, because these mRNA vaccines require ultra cold storage. And mRNA itself is a very unstable molecule. So we have to keep it at very cold temperatures when we work with it in the lab, usually at least minus 80 degrees Celsius.

Most of those ultra cold freezers that are capable of storing vaccine doses at those temperatures are located in hospitals or major medical centers. And there are not necessarily going to be a lot of these freezers in certain parts of the country. So Pfizer has been working on this. They have a delivery system that allows them to maintain the vaccine in bulk at these cold temperatures. But it is really going to be a serious challenge for many people in order to get enough of the vaccine doses when it’s being stored in the proper way, so that it’s effective when it’s finally administered to those people.

IRA FLATOW: So to those people, anybody getting that vaccine, they would almost have to go to the hospital instead of bringing the vaccine out into the community.

ANGELA RASMUSSEN: That’s right. So your local Walgreens is not likely to have a minus 80 degree freezer. So you will have to go to some place that does have that cold storage capability in order to get the vaccine.

IRA FLATOW: Is this going to be a stopgap, perhaps, do you think, until we get something better? Because we know about other vaccines being tested, correct?

ANGELA RASMUSSEN: We do. And Moderna, which also is making an mRNA vaccine, has announced that they are about to start conducting their own interim data analysis. So we may very well be looking at a situation where there are multiple vaccines available to people, which I think is really a good thing, especially if some other vaccines that are in late-stage development, such as the viral vector vaccines, are also meeting these same endpoints, that means that people will have a choice of different vaccines that may be easier to distribute in certain places.

As Dr. Dean was also saying, we need to see the breakdown of the cases that were in this interim analysis. And the FDA will need to see that when approval packages are submitted to them for consideration, there may be some of these vaccine candidates that work better in certain people than in others. For example, we know that flu shots don’t work as well in older people. So there’s a different formulation of that shot.

We may well be looking at a situation where there are multiple vaccines that are indicated for one group or another differentially. And I think overall, that’s a good thing, because we need vaccines as soon as possible. We need as many vaccines as soon as possible, and we need as many people to get vaccinated as soon as possible. So if there is a wide range of options to choose from and more doses of them, I think, overall, that’s a net win.

IRA FLATOW: We’ve heard about Johnson & Johnson and AstraZeneca working on vaccines that don’t need to be stored at over 100 degrees below zero Fahrenheit. Do you have any idea what the situation with those vaccines are?

ANGELA RASMUSSEN: Yes, so those vaccines also started Phase 3 clinical trials around the same time. Johnson & Johnson was a little bit later. Those are the viral vector vaccines that I was referring to earlier. And what they are adenoviruses, which are viruses that typically cause the common cold, that have been genetically modified so that they express the spike protein from SARS Coronavirus 2. When you get one of these, they’re replication incompetent, so they don’t replicate and cause a full-blown viral infection, the way they normally might.

But when you get those, there is some limited viral replication, and that’s what your body is responding to, except it thinks that that virus that’s replicating is actually SARS Coronavirus 2. Those vaccines don’t need to be stored at ultra cold temperatures. So they may be much more easily distributable in the population. So we should be getting data from those trials, as well, I would imagine as soon as possible, when they meet their trigger points for an interim data analysis.

IRA FLATOW: Natalie, if Pfizer gets its vaccine out the door first, let’s say, could this affect trials for these other vaccines?

NATALIE DEAN: This is a big point of discussion. How do we proceed in this setting where we may have one vaccine that may not be fully approved and may have an EUA, may just be appropriate for certain populations, may be in limited supply? It’s a very real question about whether those other trials that are ongoing will need to discontinue the placebo arm. Certainly, they’ll need to inform participants of what’s going on, and give them the option to discontinue the trial and seek alternative vaccination elsewhere.

But yeah, it’s a very open question, because it becomes much more challenging to evaluate a vaccine when you don’t have that placebo arm anymore. The alternative is we can do something called a non-inferiority trial, where we’re comparing a new vaccine against an existing vaccine that we have some good data on. But when we’re trying to show that two vaccines are quite similar, certainly to show that something is similar to 90% efficacy or even exceeds 90% efficacy, that would be very difficult. Those require much larger numbers.

So it’s a challenge. I think another source of data will be if we have some immune response data, we can start to see from the Pfizer data if there is a level of immune response that is predictive of actual protection. And that can be another source of evidence that can be used to approve other subsequent products.

IRA FLATOW: If we have multiple vaccines out in public at the same time, could one vaccine affect the effectiveness of another vaccine in one person, and another person?

NATALIE DEAN: We really don’t know what would happen if people mix vaccines. Certainly, the only people participating in these trials are only participating in one trial. They’re not receiving more than one vaccine. So it’s an open question.

IRA FLATOW: Angela, would you agree that could be something that should be looked at?

ANGELA RASMUSSEN: I think it should be looked at in the future. And we certainly have precedent for switching vaccine formulations going back decades, Initially, when the polio vaccine was developed, it was an inactivated vaccine, the Salk vaccine. And that was used to immunize kids in the US for several years, until Albert Sabin completed his vaccine trials in the Soviet Union. And then the US switched over to using the Sabin oral polio vaccine. And now, actually, we’ve switched back to using the Salk inactivated vaccine.

So there is precedent for switching back and forth between two different vaccine platforms, but I don’t think that’s something we’re going to be able to do in the short term. I don’t think if you get your first shot of a Pfizer vaccine, you should go in and get the second shot of the Moderna vaccine, or the Johnson & Johnson vaccine. I think that that’s something that we’re going to have to look at over years to see how these vaccines might interact with each other, and if there’s any harmful effects by combining two different vaccine strategies.

IRA FLATOW: I’m Ira Flatow, and this is Science Friday from WNYC Studios. Let’s talk about safety for a moment, because some of the things we’ve been hearing from the public is that they don’t want to take a vaccine, whether it’s the flu vaccine, which I think is only 50% of the population is taking it, and now any potential COVID-19 vaccine. They’re worried about the safety of the vaccine. How long will it take before we know if any vaccine is truly unsafe or not?

ANGELA RASMUSSEN: I think that’s a tough question, because normally, the Phase 3 clinical trial is not the end of the study of the vaccine. Vaccine side effects are studied once they’re also put out onto the market. And that’s because, even in a trial of tens of thousands of people, you aren’t going to be able to detect those really, really rare adverse events, the one-in-a-million type events. That has to happen once the vaccine is rolled out into the population.

So there’s always a risk from taking one of these vaccines, from taking any vaccine. But it’s probably very rare. I mean, the clinical trials are designed to detect common adverse effects, at least in the short term. So I think that we will be able to conclude that these vaccines are safe, based on these trials in the short term. But we will have to continue to monitor this.

IRA FLATOW: Natalie, do you think enough people will get vaccinated to help us get to herd immunity?

NATALIE DEAN: It’s hard to know, I mean, at first. Definitely we’re going to have limited supply. So it will be challenging. I mean, we’ll just be limited by how much is available and who we’re targeting. What we don’t know is whether that the vaccine is able to prevent infection and to reduce infectiousness. So it is possible for people to receive a vaccine, that vaccine to work at preventing disease, preventing the symptoms of disease. But that person could still be infected, and could still pose a risk to others.

So that has huge bearing on herd immunity, and how far we are towards herd immunity. So I’m very interested to see the results that come out of these trials when we take a closer look, to see whether there is any evidence, maybe among the people who become sick. Maybe they have less viral shedding. There are a lot of interesting questions that will tell us how much the vaccine will contribute to the population level control.

IRA FLATOW: Angela, as we see progress toward these other approved, available vaccines, how skeptical should the public be in weighing the major headlines we keep seeing when a new vaccine possibility comes out?

ANGELA RASMUSSEN: The most pressing challenges with these vaccines, with all of them, is the communication aspect of it. So I think it’s really important that one of the things we are communicating is that people really do need to manage their expectations. And people who are skeptical of the vaccines also should know that they will have plenty of time before these vaccines are widely available to judge how the rollout of these vaccines to the population is going.

I think that people do need to realize that even when a vaccine is approved, there’s still going to be a months-long process of actually distributing that vaccine, making sure that everybody who needs the vaccine is able to get it. So there are some real challenges still in front of us, and many of them are logistical challenges. But the bottom line is that people should be cautiously optimistic, that they should manage their expectations about when they’re going to actually be able to get the vaccine for themselves.

IRA FLATOW: Good place to end. I want to thank you both for taking time to be with us today. Dr. Angela Rasmussen, associate research scientist at Columbia’s Mailman School of Public Health in New York, Dr. Natalie Dean, assistant professor of biostatistics at the University of Florida in Gainesville. Thank you both for taking time to be with us today.

ANGELA RASMUSSEN: Thanks for having me, Ira.

NATALIE DEAN: Thank you.

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