This page summarizes findings from the Phase 3 study testing the efficacy and safety of the Pfizer BioNTech COVID-19 vaccine, BTN162b2. About 44,000 people enrolled in this study. Half of them received the BTN162b2 vaccine, while the other half received a placebo vaccine. A brief summary of the design of this study can be found in Table 1 on this website. More detailed information about the design of the study can be found on ClinicalTrials.Gov and the full protocol for the study can be found here.
Most of the data summarized on this page are from analyses that Pfizer and the US Food and Drug Administration (FDA) conducted from mid-November to early December 2020. At the time of these analyses, study participants had been followed an average of 2 months after receiving the first vaccine dose. However, some participants had been followed for over 3 months The study is continuing and the findings may change somewhat as more data are collected.
At the bottom of this page, we provide links to more detailed information prepared by Pfizer, the FDA, and the Centers for Disease Control and Prevention (CDC).
The figure below shows when the cases of COVID-19 occured in the groups that received a placebo vaccine (red line) and the BTN162b2 vaccine (blue line). The figure suggests that the BTN162b2 vaccine starts to provide protection around 12-14 days following the first dose and continues to provide protection for at least 90 days. As participants in the study are followed longer, this type of figure will give us an idea of when (or if) vaccine efficacy starts to decrease. (You can click on the figure to enlarge it.)
For seven days after receiving an injection (either the BTN162b2 vaccine or the placebo vaccine), study participants completed an electronic diary each day. The diary included a list of possible vaccine side effects. Participants were asked to check any side effects they were having that day and to provide information about the severity of the side effect. The list included both local (e.g., pain at the injection site) and systemic side effects (e.g., fever). Information reported in these diaries is presented in the figures below.
Local Vaccine Side Effects: Any Intensity
The figure below shows the percentage of participants who had local side effects of any intensity (mild, moderate, or severe). Most of these side effects were rated as mild and did not interfere with one’s daily activities. On average, these side effects lasted about 2.5 days following an injection. Participants age 56 and older were less likely to report injection site pain than younger participants.
Local Vaccine Side Effects: Moderate or Severe Intensity Only
The figure below shows the percentage of participants who had local side effects that were rated as moderate or severe in intensity. Moderate intensity was defined as pain that interfered with daily activities or a rash/swelling that was between 5 and 10 cm (about 2 to 4 inches) in size. Severe intensity was defined as pain that prevented daily activities or a rash/swelling that was greater than 10 cm (about 4 inches) in size. Participants age 56 and older were less likely than younger participants to report moderate/severe injection site pain.
Systemic Vaccine Side Effects: Any Intensity
The figure below shows the percentage of participants who had systemic side effects of any intensity (mild, moderate, or severe). On average, these side effects started 1 to 2 days after getting the vaccine and lasted 1 day. Most of the systemic side effects were reported less often by participants age 56 and older than younger participants.
Systemic Vaccine Side Effects: Moderate or Severe Intensity Only
The figure below shows the percentage of participants who had systemic side effects that were rated as moderate or severe in intensity. For fatigue, headache, muscle/joint pain, and chills, moderate intensity was defined as the side effect interfering with daily activities and severe intensity was defined as the side effect preventing activities. For diarrhea, moderate intensity was defined as 4 to 5 loose stools in 24 hours and severe intensity was defined as 6 or more loose stools in 24 hours. Participants age 56 and older were less likely than younger participants to report moderate/severe systemic side effects.
Other Potential Side Effects
In addition to completing daily diaries for 7 days after receiving each vaccine dose, participants are being followed for up to two years to determine if the BTN162b2 vaccine has any unexpected side effects. The potential side effects reported by study participants are analyzed to determine if there are differences between those who received the BTN162b2 vaccine and those who received the placebo vaccine.
As of November 14, 2020, only a few differences have been found between the two groups. Among the ~38,000 study participants (followed for an average of 2 months at this point):
- 70 people (64 in the BTN162b2 group and 6 in the placebo group) experienced lymphadenopathy (swollen lymph nodes). The FDA concluded that this is a plausible side effect of the vaccine. However, only one of the cases met the criteria for a serious adverse event.
- 4 people (all in the BTN162b2 group) developed Bell’s Palsy. One of these cases appeared 3 days after vaccination. The other three cases appeared 9, 27, and 48 days after vaccination. Bell’s Palsy is a temporary condition that can cause weakness or paralysis of facial muscles. As a result, one side of the face may droop or become stiff. None of these cases met the criteria for a serious adverse event and the FDA concluded that not enough information is available to determine if the BTN162b2 vaccine can cause Bell’s Palsy. It is possible that the small difference between the BTN162b2 group and the placebo group occurred by chance.
- 1 person in the BTN162b2 group experienced a shoulder injury. The FDA considered this a serious adverse event possibly related to vaccine administration or the vaccine itself.
Questions That Remain
Unknown Benefits/Data Gaps
- Duration of protection. Currently, only about 3,000 study participants have been followed more than 90 days after receiving their first dose of the BTN162b2 vaccine. Therefore, at this point in time, it is not possible to determine how long protection from COVID-19 is likely to last.
- Vaccine effectiveness against asymptomatic infection. More information is needed to determine if the BTN162b2 vaccine helps prevent asymptomatic infection and virus transmission, particularly among people with asymptomatic infections.
- Effectiveness in individuals previously infected with SARS-CoV-2. Fewer than 4,000 people in the Phase 3 study had evidence of a previous infection with SARS-CoV-2. Among these people, 8 developed COVID-19 during the follow-up period (1 in the BTN162b2 group and 7 in the placebo group). This suggests that previously infected individuals may benefit from being vaccinated. However, more data are needed to draw a firm conclusion.
- Effectiveness in individuals who are immunocompromised or are receiving immunosuppressant medications. There were not enough people with these conditions in the Phase 3 study to determine if the vaccine is effective in these individuals.
- Vaccine effectiveness against mortality and long-term effects of COVID-19. It is reasonable to expect that the BTN162b2 vaccine will reduce the risk of dying from COVID-19 or experiencing long-term health problems (e.g., organ damage) as a result of the disease. However, more data are needed to confirm these potential benefits. It is likely that answers to these questions will come from observational studies involving millions of people. People in observational studies are not randomized to receive a particular type of treatment. Therefore, no one would be required to get the BTN162b2 vaccine and no one would be denied the vaccine. Nonetheless, researchers can use data from observational studies to see if there are differences in health outcomes (e.g., death, hospitalization) between people who received a certain type of treatment (for example, the BTN162b2 vaccine) and those who did not.
Unknown Risks/Data Gaps
- Pregnancy and Lactation: The Phase 3 trial excluded women who were pregnant or breastfeeding at the start of the trial and female participants of child-bearing potential agreed to practice adequate conception for at least 28 days following the second vaccine dose. Most clinical trials of investigational drugs do not include pregnant women, so this is not unusual. If you would like more information about the inclusion of pregnant women in clinical trials, see this FDA Guidance document.
In spite of the exclusion of pregnant women from the Phase 3 trial, 12 women in the BTN162b group became pregnant shortly after receiving the vaccine. As of December 2, 2020, these 12 women have not reported any adverse pregnancy outcomes.
The FDA advises women who are pregnant or breastfeeding to discuss their options for vaccination with their healthcare provider.
Why might a woman who is pregnant consider getting the BTN162b vaccine? First, research suggests that women who are pregnant and contract COVID-19 may develop more severe disease than women who contract COVID-19 but are not pregnant.(See these two reports from CDC for more information 1, 2.) COVID-19 may also increase the risk of preterm birth. Being vaccinated against COVID-19 may lower these risks. Finally, certain medical conditions increase the risk of developing severe COVID-19. Therefore, it is especially important for women with any of these conditions to discuss their options for vaccination with their healthcare provider.
The information in the box below is taken directly from the FDA-approved Fact Sheet for Healthcare Providers (page 25), dated 12/2020.
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on Pfizer-BioNTech COVID-19 Vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.
Data are not available to assess the effects of Pfizer-BioNTech COVID-19 Vaccine on the breastfed infant or on milk production/excretion.
- Individuals who are immunocompromised. The FDA concluded that there is not enough information to draw conclusions about the safety and efficacy of the BTN162b2 vaccine in individuals who are immunocompromised. Individuals who are immunocompromised or on a medication that affects the immune system are advised to talk to their health care provider. More information about vaccination decisions for people with underlying medical conditions is available from the CDC.
- Adverse reactions that are very uncommon or that require longer follow-up to detect. In the Phase 3 trial, about 22,000 people received the BTN162b2 vaccine. This may not be enough to discover uncommon (and potentially serious) side effects. In addition, when the FDA issued the emergency use authorization (EUA) for the BTN162b2 vaccine in December 2020, study participants had only been followed for an average of 2 months. The FDA considered this an adequate length of follow-up for the purpose of issuing the EUA because historical data indicate that most adverse events from vaccines occur within 6 weeks following vaccination. Nonetheless, surveillance systems (including, the Vaccine Adverse Event Reporting System, VAERS, and v-safe) are in place to detect uncommon or delayed adverse events as soon as possible under the EUA.
- Vaccine-enhanced disease. Data from the Phase 3 trial suggest that the BTN162b2 vaccine helps protect against severe COVID-19. However, it is still unknown if the risk of more severe disease following vaccination may increase over time, especially if immunity decreases over time. Study participants continue to be followed to assess this potential risk.
- Severe allergic reactions. No one in the Phase 3 trial had an anaphylactic or severe allergic reaction immediately after receiving the BTN162b2 vaccine. However, since the vaccine has become available under the EUA at least six cases of anaphylactic reactions have been reported in the US. The FDA recommends that people not get the BTN162b2 vaccine if they have had a severe allergic reaction after a previous dose of the BTN162b2 vaccine or if they have had a severe allergic reaction to any of the ingredients in the vaccine. The list of ingredients in the vaccine is available in the Fact Sheet for Healthcare Providers. More information about COVID-19 vaccines and how healthcare providers can manage severe allergic reactions if they occur is available from the CDC.
- 92-page briefing document prepared by Pfizer when requesting an emergency use authorization (EUA) for the BTN162b2 vaccine
- 53-page document prepared by the FDA after reviewing the materials submitted by Pfizer
- 30-page Fact Sheet for Healthcare Providers Administering the Vaccine
- 6-page Fact Sheet for Recipients and Caregivers