This post will attempt to answer the following questions:
- What is an emergency use authorization (EUA)?
- What are the official efficacy results for the Pfizer vaccine?
- What’s the difference between efficacy and effectiveness? Does it matter?
- Were there any safety issues?
- What were the major side effects of the vaccine and how should we treat them?
I typically try to make these posts more personal for people by describing my own experience with COVID-19. I know many people feel distant from the pandemic and many have told me it really helps them to get a frontline point of view. Today I was just too excited. The reason for my elation is that I read the briefing document from the EUA analysis of the Pfizer vaccine put out by the FDA. I figured I’d summarize the report in laymen’s terms. It is a 58 page document (and that’s just the summary) and may be too much for people on the go.
An EUA (Emergency Use Authorization) is a rule that allows medications, vaccines, or devices to be used in an emergency situation to diagnose, treat, or prevent a serious or life-threatening condition before they get complete approval by the FDA. It is designed for when there are no adequate available alternatives. Certainly a COVID vaccine falls under this definition.
On November 20th, Pfizer sent the data from their phase 3 trial of almost 44,000 participants to the FDA for analysis. As an aside, the FDA usually takes a long time to analyze the data for bureaucratic reasons but the red tape has all been cut and all efforts have been focused on the vaccines. This is one of the reasons why the approval process is moving so fast and why the speed shouldn’t alarm us. The science is not being rushed, only the bureaucracy.
The EUA included data on safety and efficacy from an interim analysis of about 36 of the 44,000 subjects. This analysis was triggered when a certain number of infections had happened and was planned before the study began. The analysis evaluated both efficacy and short term safety of the vaccine.
Insert drum roll here.
There were 162 cases of COVID-19 in the placebo group and 8 in the vaccine group. A quick back of the napkin math and you can see that 8 is 5% of 162. This is where the 95% efficacy comes from. To make the news even better, when they analyzed the data in different groups such as different ages, races, gender, and comorbidities, the results were just as good.
Efficacy vs. Effectiveness
I have heard these two terms used interchangeably by the media and even public health officials recently which is a bit confusing. These are not the same thing. This is not just a semantic problem, it can lead to false exceptions for the vaccine.
Efficacy is measured by seeing how many cases of COVID-19 occurred in the vaccine group and the placebo group under ideal (e.g. randomized controlled trial) conditions. The ration of vaccine cases to total cases is the efficacy.
Effectiveness is the ability of vaccine to prevent outcomes of interest in the “real world”.
There are many reasons to assume that the vaccine will have lower effectiveness than efficacy. This is especially true with mRNA vaccines which are chemically unstable. Unstable does not mean they are dangerous in case you were worried. It means the vaccine is more likely to break down and lose effectiveness. It’s the instability that requires it to be stored at very cold temperatures. There is a concern that without the strict oversight and logistics genius of the research teams running the trials the handling of the vaccine may be substandard decreasing effectiveness. There may be other factors that lower effectiveness as well such as people not showing up for their second dose (this has been a problem with other 2 dose vaccines like hepatitis A).
The good news is that, with an efficacy of 95%, effectiveness can drop quite a bit and the vaccine would still have a huge impact.
Safety data was also encouraging but people need to be aware that minor side effects were very common. Almost everyone (84%) had some soreness at the injection site and most had mild fatigue (63%) and headache (55%). Mild muscle pain (38%), chills (24%), joint pains (24%), and fevers (1%) were less common. These side effects only lasted between 1 and 2 days in almost everyone and are seen with other vaccinations as well.
Keep in mind that these mild side effects are actually a good sign. They indicate an activated immune response to the vaccine which is the goal. If the immune response is strong enough to cause symptoms it is likely strong enough to elicit protection. These symptoms can be treated with Tylenol although I would be hesitant to recommend anti inflammatory medications for fear that they may blunt the immune response and make the vaccine less effective.
The only serious side effects were 4 cases of Bell’s palsy in the vaccine group. Bell’s palsy is non life-threatening condition where the nerve to the muscles of one side of the lower face stops working leading to difficulty with facial expression. It is a relatively common condition that happens often without any trigger. It is not uncommon for a random population of >20,000 people to have 4 cases of Bell’s palsy. It is therefore not clear if this was a result of the vaccine itself or a coincidence but it will need monitoring.
To sum up, this vaccine had very high efficacy. The data is better than can be expected and scientists around the world are giddy. The EUA was approved and the factories are producing vaccine as we speak. The data from the Moderna vaccine should be coming soon as well and is expected to be similar.
It is important to note that this data only shows that there will be fewer symptomatic infections in a group of vaccinated vs unvaccinated individuals. There is no data on whether or not the vaccine decreases asymptomatic infections or disease transmission. It may be that all those people who did not get infections just dropped down a notch from symptomatic to asymptomatic but were still contagious. This is one of the reasons that a vaccinated individual should still wear a mask. It is also not known how long the effect will last. With time, more data can be collected to answer these questions.
The real test of the effectiveness of the vaccine is a sustained drop in case numbers, hospitalizations and deaths. When we see this after widespread vaccine adoption, the end will be near. We’re not there yet but we just got a lot closer.