The Pfizer-BioNtech vaccine: Good news and what we still don’t know
The US Food and Drug Administration recently released their briefing document containing detailed data from the Pfizer-BioNTech vaccine phase 3 trials, and the agency’s advisory panel is discussing the vaccine this week. (Author’s note: The FDA approved the vaccine after this blog was originally published.) Ever since the initial press release from Pfizer came out, the medical community has been waiting for more detailed results to better analyze the vaccine’s effectiveness and safety. Here’s what the briefing document shows.
The (very) good news!
The 94.5% effectiveness rate touted in the original press release holds up in the detailed data, even across subsets of people especially vulnerable to Covid-19. Two months after the second vaccine dose, there were 9 cases of Covid-19 in the vaccine group (18,559 people) and 169 cases in the placebo group (18,708 people), which is an efficacy rate of 94.6%. Among those older than 55, the vaccine was was 93.8% effective. Among those with comorbidities that put them at risk for Covid-19 such as obesity and diabetes, the vaccine was 95.4% effective. The vaccine also showed similar or higher efficacy in racial groups that have been disproportionately affected by Covid-19 as well. Even in people over 65 with comorbidities, the vaccine was 91.7% effective in preventing symptomatic Covid-19.
The absolute reduction in risk from the vaccine is 0.852%, as 0.9% of the placebo group got Covid-19 and 0.048% of the control group got Covid-19. This makes the “number needed to vaccinate” 177 to prevent one case of Covid-19.
There are a few subgroups in which there were not enough cases in the sample to determine effectiveness. For example, in the age group of people 75 and older, no one in the vaccine group got Covid-19 and five people in the placebo group got Covid-19. This looks promising, but the small number of cases overall precludes making strong conclusions about this subgroup specifically. Similarly, there were too few cases among people under 18, Asian Americans, Native Americans, people of mixed race, and those with the specific comorbidities of cardiovascular disease or malignancy. This is not to say the vaccine “doesn’t work” in these populations, only that there isn’t enough statistical power in this trial to show efficacy within these specific subgroups.
The small number of severe Covid-19 cases in the sample also makes it more difficult to know how well the vaccine protects against severe Covid-19. Looking only at severe cases that occurred after the second dose, there were three cases in the placebo group and one in the vaccine group — not enough data to know. Looking at all severe cases that occurred after the first vaccine dose, the data are more encouraging. After the first dose there were nine severe cases in the placebo group (seven were hospitalized, three went to the ICU) and one severe case in the vaccine group (not hospitalized), which shows 88.9% efficacy for the vaccine.
Overall, the speed at which we’ve been able to develop and test Covid-19 vaccines is incredible, and those who have worked on the vaccines (and mRNA technology in prior years) and supported the efforts should be commended.
“I think if you asked 100 scientists in January, ‘Do you think that by the end of the year we will have done two large prospective placebo-controlled trials of 30,000-40,000 people…and have the kind of efficacy we’re seeing,’ no one would have believed that. It’s remarkable!” said Dr. Paul Offit, vaccine specialist and FDA vaccine advisory committee member, in a video interview with ZDoggMD.
How safe is it?
Safety is obviously an enormous concern for this vaccine, as this will ideally be taken by millions of people nationwide. The news on the safety front is also good, because there were no unusual or severe adverse events in the vaccine trial. The majority of vaccine side effects occur within two months of taking the vaccine, and the FDA (even under extreme political pressure to move faster) insisted on two months of safety data.
That said, there were fairly common mild side effects from the vaccine, which should be made clear to the public. In the vaccine group, 84.1% of people experienced injection site pain, 62.9% had fatigue, 55.1% had a headache, 38.3% had muscle pain, 31.9% had chills, and 14.2% had fever. Mild swelling of the lymph nodes occurred more often in the placebo group (58 more cases) but still very rare. The rate of mild adverse events was higher in younger trial participants, with those in the below 55 age group having a greater rate than those over 55.
These side effects show that the vaccine is working and producing an immune response, but may make people hesitant about getting the second shot, or lead people to think that the vaccine gives you Covid-19. Pfizer also recently put out a warning that people with severe allergies to food or medications should not take the vaccine, as it may cause an allergic reaction. Doctors and public health officials need to be transparent about the possible side effects, so as not to lose more public trust in vaccines.
In terms of severe adverse events, the report noted one case of shoulder injury and one case of swelling lymph nodes that could be related to the vaccine. There were also four cases of Bell’s palsy (muscle weakness in half of the face) in the vaccine group and none in the placebo group. The FDA did not perceive this as a definite causal effect of the vaccine because the number of cases was not more frequent than expected in the general population. However, others disagreed, saying that the rate of Bell’s Palsy in the vaccine group of 21/100,000 is greater than the general population rate of 13-15/100,000. In the report, the FDA recommends “surveillance for cases of Bell’s palsy with deployment of the vaccine into larger populations.” Fortunately, Bell’s Palsy usually resolves within a few months, but we still need to be clear and honest about the potential side effects.
What about very rare side effects that would not be noticed even in a trial of 35,000 people? As Dr. Gideon Meyerowitz-Katz, an epidemiologist working in chronic disease in Sydney, Australia, writes, “We do have a mechanism to detect these, called a phase 4 trial. This is the monitoring that looks at the safety of vaccines in a population once they have already been licensed and exists to make sure we haven’t missed anything concerning.” As we distribute the vaccine, making sure that we track adverse events in vaccine recipients is essential to pick up on any very rare side effects. Meyerowitz-Katz also points out, “For anyone over the age of 20, the risk of death from Covid-19 infection is higher than one in 20,000, which means that even without knowing everything, we can be pretty sure at this point that the vaccines will be safer than the disease itself.”
What we still don’t know
The FDA report is very clear on what the Pfizer trial tells us and does not tell us. The vaccine was not tested in children or pregnant or nursing women, so we don’t know the effectiveness or potential side effects for these populations. Because the trial ended after two months post-vaccination, we don’t know exactly how long the vaccine protects people against Covid-19. Hopefully, the immunity will be much longer than two months, but we don’t have data on that yet. We also don’t know whether the vaccine protects specifically against “long Covid” or Covid deaths, because there weren’t enough cases of these in the trial to conclude.
The trial was designed to show vaccine effectiveness against Covid-19 by looking at “incident cases”: people with symptoms who were diagnosed with Covid-19. However, the trial does not tell us if the vaccine prevents someone from spreading Covid-19 to someone else asymptomatically. This means we will still need to wear masks and physically distancing from others until enough people have received the vaccine. Still, the very encouraging efficacy and safety data for this vaccine provides us a light at the end of the tunnel, one that is desperately needed.