
==== Front
Infect Dis Ther
Infect Dis Ther
Infectious Diseases and Therapy
2193-8229
2193-6382
Springer Healthcare Cheshire

39180645
1019
10.1007/s40121-024-01019-9
Letter
A Letter to the Editor Regarding ‘Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-analysis Using the GRADE Framework’
http://orcid.org/0000-0001-7274-9641
Volkman Hannah R. hannah.volkman@pfizer.com

Nguyen Jennifer L.
Jodar Luis
McLaughlin John M.
grid.410513.2 0000 0000 8800 7493 Pfizer Inc., 66 Hudson Blvd. E, New York, NY 10001 USA
24 8 2024
24 8 2024
10 2024
13 10 22032206
5 4 2024
2 7 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Keywords

mRNA vaccines
SARS-CoV-2
Vaccine effectiveness
http://dx.doi.org/10.13039/100004319 Pfizer issue-copyright-statement© Springer Healthcare Ltd., part of Springer Nature 2024
==== Body
pmcDear Editor,

We have several serious concerns regarding the systematic review and meta-analysis by Kavikondala et al. [1] which compared the vaccine effectiveness (VE) of mRNA-1273 and BNT162b2 in adults aged ≥ 50 years.

First, the authors based their meta-analysis on crude data when adjusted VE estimates were available. This approach makes interpretation difficult and is in conflict with World Health Organization guidance on the evaluation of COVID-19 vaccine effectiveness, which states that “it is important that all VE evaluations account for confounding as far as is possible” [2]. This major error in the analysis phase stripped away all adjustments for bias and confounding made in the original studies. This flawed approach also frequently resulted in incorrect estimates that not only greatly exaggerated the numerical differences in VE between the two vaccines but also led to conclusions that directly contradicted those of the original study authors in many instances. As a brief example of this (see Supplementary Appendix for additional details), wherein one of the original studies concluded “there was no difference in VE between BNT162b2 versus mRNA-1273 recipients [3]” based on their reported adjusted VE results, Kavikondala et al. instead calculated and used a 63% crude relative difference in VE as their point estimate for this study in the meta-analysis. This mistake—where the original studies found no difference in VE between these two vaccines, yet the random effects risk ratios calculated by Kavikondala et al. significantly favored mRNA-1273—occurred in 20/54 (37%) of all VE estimates (from the 24 included studies) reported in Fig. 3a–e. In addition, there were many eligible studies that were missed in this systematic review (i.e., at least 14 studies) and extensive errors in data extraction. These concerns are described in detail in the Supplementary Appendix.

Second, the authors set out to compare mRNA-1273 and BNT162b2, so they should have included only head-to-head VE estimates. Comparative estimates better account for potential brand-specific differences in population characteristics of vaccine recipients (e.g., age or COVID-19 risk status) and timing of vaccine availability [4–6]. However, of the 24 included studies, only three were head-to-head comparisons, and of these three, only one was conducted during the Omicron era.

Accordingly, our final concern is that most of the studies included in the review were not contemporary in that they (i) evaluated time periods before the emergence of the Omicron variant, and (ii) assessed only the effectiveness of wild-type vaccines. Pre-Omicron studies do not reflect the current setting of high levels of population immunity against SARS-CoV-2 stemming from vaccination and prior infection, where up to 98% of populations in most countries now have some degree of protective immunity [7, 8]. Of the 24 studies included in their review, only three (13%) contributed data from the Omicron era and none evaluated effectiveness of variant-adapted vaccines, which have largely replaced wild-type vaccines globally since autumn 2022 [9, 10].

In the most recent head-to-head studies comparing the effectiveness of mRNA-1273 and BNT162b2 booster doses during contemporary periods of Omicron predominance (which includes more recent studies that were published after the review’s search period) [11–18], there is no evidence of a difference in effectiveness between the two mRNA COVID-19 vaccines.

In summary, the meta-analysis by Kavikondala et al. comparing VE of mRNA-1273 and BNT162b2 is based on both inaccurate and out-of-date data. Although adjusted VE estimates were available, the authors instead inappropriately used crude data, and most of the included studies were not designed for head-to-head comparisons. We are concerned that this methodology confounded the interpretation of the results, as evidenced by numerous instances where Kavikondala et al. arrived at conclusions that contradicted the findings and interpretation reported by the original study authors. Further, the review relied primarily on data from older studies of wild-type vaccines that were conducted prior to the emergence of the Omicron variant. As a result, the findings of the review have little relevance to the current post-pandemic world. Contemporaneous, post-pandemic data from the Omicron era that compare head-to-head effectiveness of booster doses have not shown a difference in VE between mRNA-1273 and BNT162b2.

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file1 (PDF 174 KB)

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

All authors contributed to the study conception and design. Analysis was performed by Hannah R. Volkman and Jennifer L. Nguyen. The first draft of the manuscript was written by Hannah R. Volkman, and all authors contributed to review and editing. All authors read and approved the final manuscript.

Funding

This work was funded by Pfizer, Inc. No funding or sponsorship was received for the publication of this Letter to the Editor.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the generation of the letter.

Declarations

Conflict of Interest

Hannah R. Volkman, Jennifer L. Nguyen, Luis Jodar, and John M. McLaughlin declare employment and/or holding stocks and/or options at Pfizer Inc. during the conduct of the study. The authors declare no non-financial competing interests.

Ethical Approval

This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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