Boston—Both of the messenger RNA vaccines used in the United States work well, but a new study finds that, in a head-to-head comparison, the Moderna product is more effective than the Pfizer-BioNTech product.

The report in the New England Journal of Medicine was based on an examination of U.S. military veterans who had received each vaccine. Overall, both vaccines were determined to be highly effective in preventing COVID-19 outcomes such as documented infection, hospitalization, and death.

The Moderna vaccine, however, 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 study team led by researchers from the Harvard T.H. Chan School of Public Health, Brigham and Women's Hospital and the U.S. Department of Veterans Affairs (VA).

'Both vaccines are incredibly effective, with only rare breakthrough cases," said  J.P. Casas, MD, PhD, an epidemiologist and associate professor with Brigham and Women's Hospital and Harvard Medical School and executive director of the VA's Million Veteran Program for genetics and health research. "But regardless of the predominant strain—Alpha earlier and then Delta later—Moderna was shown to be slightly more effective."

The comparative effectiveness study was designed to answer a persistent question: Which of the two mRNA vaccines is more effective. To determine that, effectiveness was measured with five COVID-related criteria:

• Documented COVID-19
• Symptomatic disease
• Hospitalization
• ICU admission
• Death

For the investigation, the authors used electronic health records of VA patients who received one of the two COVID-19 vaccines between early January 2021 and mid-May 2021. The first phase of the research focused on the Alpha variant that was predominant at the time. Recipients of the two vaccines, 219,842 who got the Pfizer vaccine compared to the same number of Moderna recipients, were matched based on a range of clinical and demographic factors that could affect outcomes.

Results indicate that 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, an excess of 1.23 cases of documented infection per 1,000 people in the Pfizer group.

Smaller differences were with the other criteria: 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.

Similar results were determined in an additional research phase during a time frame when the Delta variant was the primary COVID-19 strain. Excess risk of documented infection over 12 weeks was 6.54 events per 1,000 people for the Pfizer vaccine, compared with Moderna. The supplementary research involved a shorter time frame, only analyzed infection as an outcome, and was considered less precise because a smaller number of veterans were eligible for this analysis.

"Given the high effectiveness of both the Moderna and Pfizer vaccines, confirmed by our study, either one is recommended to any individual offered a choice between the two," said the study's first author, Barbra A. Dickerman, PhD, an epidemiology instructor with the Harvard T.H. Chan School of Public Health. "However, while the estimated differences in effectiveness were small on an absolute scale, they may be meaningful when considering the large population scale at which these vaccines are deployed. This information may be helpful for larger decision-making bodies."

Researchers chose to do the research using the very large VA records system because, with millions of patients nationwide, the system allowed a very large sample size. That meant that even small differences in effectiveness between the Pfizer and Moderna vaccines could be pinpointed.

The VA databases also enable the study team to precisely characterize recipients of each vaccine type and closely match them on age, sex, race, geographic location, and other attributes that could affect COVID-19-related outcomes.

"After this careful matching, we found that the two vaccine groups were extremely similar in terms of variables with respect to an extensive set of demographic, geographic, and health-related attributes," Dr. Dickerman said. "This allowed our observational analysis to produce exceptionally credible results during a global emergency when answers are needed fast and randomized trials can be impractical."

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.