Pfizer announced this week that early data show its vaccine to be “more than 90 percent effective.” But what does that actually mean? And does it change the timeline for a return to “normal life”?
Stephen Thomas, the chief of infectious disease at SUNY Upstate Medical University and the lead principal investigator of the Pfizer vaccine trial, answers questions on the podcast Social Distance from staff writer James Hamblin and producer Katherine Wells.
Listen to their conversation here:
What follows is a transcript of their conversation, edited and condensed for clarity:
James Hamblin: Your hospital is one of many sites for the clinical trial of the Pfizer COVID-19 vaccine. Could you lay out the basic facts here?
Stephen Thomas: Pfizer and BioNTech have partnered to develop a COVID-19 vaccine. There is a Phase III trial going on globally—about 140 sites around the globe. And SUNY Upstate in Syracuse, where I work, is one of those sites. We’ve been enrolling volunteers since July.
Hamblin: And now you are the lead principal investigator for this global trial.
Thomas: Each of those 140 or so sites will have a principal investigator: the clinician who takes responsibility for the conduct of the trial at that site. And then it’s not unusual in these global programs for the sponsor to select someone that is outside of the company to assist them in the compilation and review of data, prior to submission to the regulatory authorities.
Katherine Wells: Can I ask you about that relationship? Are you independent of them, or do you now sort of work for Pfizer?
Thomas: No, I’m independent. Which is one of the reasons that companies will select somebody like myself who is independent: so that an objective set of eyes can look at the information.
Hamblin: It’s wonderful you find yourself in this position to help us understand what to make of this news, which sounds very good. The 90 percent number: How big of a deal should people make of that at this point?
Thomas: I personally think it’s a huge deal, and I think that it should provide people with a great deal of measured and cautious optimism that we can make a safe and efficacious COVID-19 vaccine. It is the first step among multiple steps that we need to go through to get to the finish line.
If this step didn’t work it would have been tragic, but that didn’t happen. And if you talk to a lot of vaccine developers and immunologists and clinicians, I think many of them would say that “more than 90 percent” exceeds expectations.
Hamblin: You’ve had about 44,000 people who have enrolled in the study. Half of them got the placebo injected into them, and half got this test vaccine. They don’t know what they got. Their doctors don’t know what they got. It’s double-blinded. And then people have been tested subsequently for the virus, and only 94 of those 44,000 people tested positive.
Thomas: Right—you enroll people in all these different locations around the world who are at risk for infection with SARS-CoV-2 and developing COVID-19 disease. You randomly assigned half of them to the vaccine, and randomly assigned half of them to placebo. And then you follow them. They fill out symptom diary cards, and when somebody alerts you to a symptom which is consistent with COVID-19, we investigate. They ended up having 94 cases. And then an external group that is unblinded can then look at: Well, where do those cases fall? Do they fall in the vaccine group, or do they fall in the group of people who received placebo? And they count them up, do some math—and fortunately in this case, there was great benefit from vaccination.
Wells: How do you get to “90 percent effective”?
Thomas: So there’s a difference between efficacy and effectiveness. Efficacy is a number: in this case, greater than 90 percent. It represents the percent reduction of disease in the people who received the vaccine compared to those people who received placebo.
That’s efficacy. And efficacy is a term that applies to controlled environments like a clinical trial. Effectiveness is efficacy translated into the real world: the practicalities of everyday life outside of a clinical trial. Efficacy is more of an individual level, whereas effectiveness is almost at a sort of a population level. They reported efficacy, which is the data within the context of the clinical trial.
Wells: When I’m reading this number—90 percent—as a layperson who hopes to get the vaccine someday, does that mean that if I get this vaccine, there’s only a 10 percent chance I’ll get COVID-19?
Thomas: You’re pretty close. What it means is that if you were to get the vaccine, your risk of getting COVID-19 is reduced by 90 percent. For context, the 2019–2020 influenza vaccine had an efficacy of 45 percent. So this is more than double that, and we know that flu vaccines have a great deal of benefit in terms of morbidity and mortality in the United States every year. So, again, this is good news.
Hamblin: Dr. Fauci had floated the possibility months ago of a vaccine being 50 or 60 percent effective. Were you surprised to see a number this high?
Thomas: Yes; I was very pleasantly surprised when I found out. And I found out the way everyone else did, through the press release.
Hamblin: Why release this number before the study is done? Before there’s data that everyone can see and share?
Thomas: Well, I don’t think that this is an unusual process. Lots of big Phase III trials like this will have interim analyses planned—especially when you get into trials with tens of thousands of people, that are going to cost hundreds of millions of dollars to execute.
But the other thing that I would mention is: This is a two-year experiment. And there’s a reason that it’s two years. There’s lots of really important questions that are going to need time to answer. I don’t speak for the company, but I personally think it is important that this data be known and not held until the end of a two-year period.
Wells: If this vaccine is 90 percent effective, that sounds pretty good. When can we see it in use?
Thomas: There’s still multiple steps and a lot of process. Pfizer reported the efficacy data. They made statements that there were no concerning safety signals, but the FDA needs to see the data, and they will do a very deep dive into the data. In the coming days and weeks, Pfizer is going to compile all this information for the FDA: their efficacy data, their safety data, their manufacturing-process information. Then the FDA is going to ask questions, deliberate, and ultimately make a decision whether or not to issue an emergency-use authorization. That will allow distribution of the vaccine outside of the context of a clinical trial, but there still is a huge logistical lift that must occur for millions and millions of doses to be distributed.
Wells: What are the main logistical obstacles? What makes this hard to make and distribute?
Thomas: The scale and the kinetics of distribution required in the midst of a pandemic are a challenge, in and of itself. This particular vaccine currently has a requirement to be stored at a very cold temperature. It needs very specific types of freezers that go to very, very cold temperatures.
Wells: Does this change anything about the timeline? Is this speeding things up? Or are we on the track we’ve all been hearing about, which is: approval by the end of the year, widespread availability not until maybe late spring or summer next year?
Thomas: I’ve always been on that timeline, and I remain on that exact timeline. This positive news keeps this vaccine on the pathway that has been set for it. I don’t see widespread rollout of vaccines throughout the country to those first-tier recipients happening before the first quarter of 2021, or into the second quarter of 2021.
Wells: Okay, so ... great news. Doesn’t change anything. Can I ask you one more logistical question? You mentioned that people have to be willing to take the vaccine. We had vaccine skepticism long before COVID-19, but the accelerated timeline and terms like “warp speed” have made even people who trust vaccines have questions about things that we don’t know yet. We hear headlines every now and then about adverse reactions, and it sounds scary. Is this the kind of thing that we could find out years from now? How concerned should I be about adverse reactions, and how much we don’t know yet?
Thomas: With any medication or vaccine, there is always a risk-benefit [ratio]. Nothing is 100 percent effective, and nothing is 100 percent without risk. But with the process of developing vaccines and drugs, a lot of those risks can be identified early on. I know that people are concerned about the speed of this development—but I do think that there are some things that people may or may not realize which have contributed to the speed.
The first is that vaccines typically take a long time to develop, because it’s very, very expensive to develop a vaccine. It costs easily over a billion dollars—that’s kind of the historical benchmark. And so companies, when they’re developing vaccines, take a very pragmatic and very sequential approach to mitigate financial risk. What has happened with COVID-19 is that, in the case of Pfizer, they’ve underwritten their own financial risk. In the case of Operation Warp Speed, the U.S. taxpayer has underwritten the financial risk. And so processes that typically occur sequentially can now occur in parallel, and that can really shave off a lot of time. And that’s an acceptable risk, especially in the face of a pandemic, because it is not a safety risk.
The second thing is: For a lot of these vaccines that are in advanced development right now, this is not the first time that those [vaccine] platforms—messenger RNA or adenovirus vectored or chimp adenovirus vectored, all these different types of platforms—this is not the first time that they’ve been in humans. These are vaccine platforms that have been used to try to develop other types of vaccines, whether it be Ebola, influenza, Zika, or other types of vaccines. Hundreds and thousands of other people have already received these types of vaccines before, so folks weren’t really starting from zero.
And the third is that: In the past, the FDA review timelines could be substantial. For many years, it was up to two years from the time that a sponsor would submit a packet for consideration before they would get an answer. Now that timeline is, on average, 10 months or less. And in the context of a pandemic—and we saw this with Ebola and Zika—regulatory agencies are in very close contact with the sponsors, so the reviews are occurring at a very quick pace. I know that it’s fast, but at least from my perspective, I have not seen any safety risks. I have not seen any corners that have been cut in the process. I have not seen any sponsor not using these outside oversight groups, etcetera. So I understand the concern—but I think people should have confidence that if the FDA signs off on the vaccine as safe and effective, then they should have confidence that there’s the data to support that.
Hamblin: The big picture of this is that 90 percent effectiveness might not matter in terms of changing the timeline to distribution—to when you can get a vaccine. But it could make a big difference to when the pandemic ends. If you have a 50 percent–effective vaccine versus 90 percent, you can more quickly whittle things down, and maybe even people will be more likely to take the vaccine. That changes their own risk-benefit calculation. It seems to me this is really significant news in terms of the timeline to return to “normal life.”
Thomas: I think you’re right. There’s a significant proportion of folks who do not get the influenza vaccine, with the rationale that Well, it’s a flip of a coin; it’s 45 or 50 percent. I’ll take my chances. I think that 90 percent efficacy, if that performance holds, will do a lot to allay some fears and motivate folks to get vaccinated. I also think you’re correct that—if we have a vaccine which is 90 percent efficacious and widely distributed, if the uptake is great, and we vaccinate in addition to increasing the consistency of of public-health interventions like masking and social distancing—I believe that we could make very drastic strides in flattening the nation’s curve.