Question: Now that Pfizer has been approved for 12-15 year olds, I’m being asked for some talking points on how we can trust the findings, when the trial only had 2260 youth enrolled (half of which I assume received a placebo?). Can you give an overview of why we can extrapolate the risk/benefit ratio of the adult population to that of young teens?

Answer: For the sake of time today, I’m going to focus on providing a brief overview of the study.  Tomorrow, I’ll aim to more directly answer your question on risk/benefit overview, which is an area well-described during yesterday’s meeting of the Advisory Committee on Immunization Practices’ (ACIP).  

Study overview: [for more information, see FDA fact sheet and ACIP slides] After safety and efficacy of the Pfizer vaccine were proven in ages 16+, Pfizer expanded its study protocol to include those ages 12-15.  The study was designed to examine in younger adolescents three key issues: 

1. Whether the vaccine was safe: To assess safety, researchers conducted active surveillance of all adolescents in the trial–  All 12-15 year olds had e-diaries to capture solicited events (N=2260) and a random subset of 16-25 year olds had e-diaries (N=1097) in order to capture events and make comparisons by age.  98% of study participants had at least 1 month of follow-up time for the interim analysis, with the majority having between 2-3 months of follow-up time.  Researchers found that reactogenicity (vaccine side effects) among adolescents ages 12-15 was similar to that among those ages 16-25 and was well tolerated.  Pain at the injection site, fatigue, headaches, chills, joint pain and muscle pain, and fever were the most common events.  Swelling of the lymph nodes (lymphadenopathy) was associated with vaccination and occurred in 8 participants (7 vaccinated and 1 placebo). There were five serious side effects in the vaccinated group and two in placebo, and no reported severe adverse outcomes.  Of the five severe side effects in the vaccinated group, none were linked to the vaccination.  Four (4) of the five events were related to psychiatric disorders, including depression, which were present in the participants before the trial. The vaccine is safe for adolescents.
2. Whether the vaccine prevented symptomatic infection: Researchers compared cases between vaccinated and placebo groups at 7+ days post second dose.  Among participants who had no history of COVID-19, zero (0) cases were observed in the vaccinated group while 16 cases were observed in the placebo group.  Including participants who had a history of previous infection, zero (0) cases were observed in the vaccinated group while 18 cases were observed in the placebo group.  Vaccine efficacy is 100% (95% CI 75%-100%).  The vaccine has high efficacy among adolescents.
3. The degree to which the vaccine elicited an immune response: To further assess vaccine efficacy, researchers invited a random set of participants to provide blood for lab testing to detect the level of antibodies present.  As shown in Figure 1, the vaccine produced a strong immune response on adolescents, and the response was even stronger among 12-15 year olds.  This is another strong indication that the vaccine has high efficacy among adolescents.

Figure 1. Immune response by vaccination status and age (pulled from ACIP slide deck)