Which COVID-19 vaccine works better, Pfizer or Moderna?

Dec. 3, 2021

In the first head-to-head comparison of the effectiveness of the Pfizer-BioNTech and Moderna COVID-19 vaccines, researchers examined the electronic health records of veterans who had received each vaccine. Both vaccines were highly effective in preventing COVID-19 outcomes such as documented infection, hospitalization, and death according to a press release from the Veterans Affairs.

However, the Moderna vaccine was found to offer an increased level of protection, including a 21% lower risk of documented infection and 41% lower risk of hospitalization, according to the research team, whose findings were published on December 1, 2021, in the New England Journal of Medicine.

Researchers designed their comparative effectiveness study to address the previously unanswered question of which of the two mRNA vaccines is more effective. Effectiveness was measured in terms of five COVID-related outcomes: documented COVID-19, symptomatic disease, hospitalization, ICU admission, and death. The investigators relied on the electronic health records of U.S. veterans who received one of the two COVID-19 vaccines between early January 2021 and mid-May 2021.

As initially designed, the research focused on the Alpha variant that predominated at the time. The study matched 219,842 recipients of the Pfizer vaccine to the same number of recipients of the Moderna vaccine. The two groups were matched based on a variety of clinical and demographic factors that could affect outcomes.

Over the study’s 24-week follow-up period, the estimated risk of documented infection was 4.52 events per 1,000 people in the Moderna vaccine group and 5.75 per 1,000 in the Pfizer group. This represents an excess of 1.23 cases of documented infection per 1,000 people in the Pfizer group. The investigators also observed an excess of symptomatic COVID-19 (0.44 events), hospitalization (0.55 events), ICU admission (0.10 events), and death (0.02 events) per 1,000 people in the Pfizer group relative to the Moderna group, but these differences were smaller. 

This pattern of a lower risk for Moderna held up in an additional phase of research covering a time frame with Delta as the main strain. In this comparison, excess risk of documented infection over 12 weeks was 6.54 events per 1,000 people for the Pfizer vaccine, compared to Moderna. Given the shorter time frame available for this supplementary research, infection was the only outcome researchers analyzed. Also, the estimates were considered less precise because a smaller number of individuals were eligible for this analysis.

Randomized trials comparing the mRNA vaccines against placebos had previously shown both vaccines to be very effective against symptomatic COVID-19 infection (95% effectiveness for Pfizer-BioNTech, 94% for Moderna), and similar benefits were observed in real-world vaccine use.

The expansive VA records system, covering millions of patients nationwide, supported a very large sample size. This, in turn, allowed the study to identify even small differences in effectiveness between the Pfizer and Moderna vaccines.

VA release

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