madeleineshort

Would you please summarize vaccine safety information?

Question: Now that the first of the vaccines is becoming available in the U.S., can you summarize what we know and don’t know about the vaccines’ safety? How were the clinical trials processes applied for these vaccines (Pfizer, Moderna, Astra-Zaneca, others?)? What incidents occurred during these trials? What is the probability of experiencing side effects or adverse reactions? What types of side effects are associated with the vaccine at time of vaccination? Later on?

Answer: So many related questions!  I’m going to focus answers on the Pfizer and Moderna vaccines since they are moving forward more quickly than others with more detailed information available, especially related to side effects.  Information included herein is pulled largely from: FDA review of the Moderna vaccine, FDA review of the Pfizer vaccine, and the peer reviewed Pfizer study recently published in the New England Journal of Medicine, Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine (Figure 1). 

Vaccine Development: All SARS-CoV-2 vaccine candidates have followed the same basic process– cell culture study, animal study, small human trial, large human trial (see Q&A of 5/13).  At each step, safety and efficacy is assessed.  If serious adverse events occur at any step, the study is halted.  Loads of vaccine candidates don’t ever make it to market due to safety concerns and/or lack of efficacy.  And even after a vaccine is authorized/approved, safety continues to be monitored (described in Q&A of 7/22).  When it comes to large-scale human trials, scientists use the randomized control trial (RCT) study design, which allows them to compare what happens to people who receive the vaccine with those who receive a placebo.  Pfizer and Moderna both employed RCT for their large-scale human studies.  

Serious Adverse Events: Adverse events considered plausibly linked to vaccination generally start within 6 weeks of vaccine receipt.  Pfizer and Moderna data span 2 months after the 2nd vaccine dose, so we have a pretty good idea of their safety profile.  For both vaccines, serious adverse events are rare.

  • As reported in the NEJM, “Four related serious adverse events were reported among BNT162b2 [Pfizer vaccine] recipients (shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the vaccine or placebo.”  
  • And as reported by the FDA’s review of Moderna, “13 deaths were reported (6 vaccine, 7 placebo)… These deaths represent events and rates that occur in the general population of individuals in these age groups…. Among participants who received at least one dose of vaccine or placebo (N=30,351), the proportion of participants who reported at least one serious adverse event from dose 1 to the primary analysis cutoff date (November 25, 2020) was 1% in the mRNA-1273 group and 1% in the placebo group.”

Side Effects: Though serious adverse events are rare, several non-serious side effects are common:

  • FDA writes of the Pfizer vaccine, “The most common solicited adverse reactions were injection site reactions (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%)…. Among non-serious unsolicited adverse events, there was a numerical imbalance of four cases of Bell’s palsy in the vaccine group compared with no cases in the placebo group, though the four cases in the vaccine group do not represent a frequency above that expected in the general population.”  
  • FDA writes of the Moderna vaccine, “The most common solicited adverse reactions associated with mRNA-1273 were injection site pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%)… lymphadenopathy (axillary swelling and tenderness of the vaccination arm) was reported as an unsolicited event in 173 participants (1.1%) in the vaccine group and 95 participants (0.63%) in the placebo group… there were three reports of facial paralysis (Bell’s palsy) in the vaccine group and one in the placebo group. Currently available information is insufficient to determine a causal relationship with the vaccine.”      

Figure 1. Pfizer Research Summary (from NEJM)