Relative efficacy of varicella vaccines: network meta-analysis of randomized controlled trials

Abstract

Objective

Although varicella vaccination is highly effective, no head-to-head randomized controlled trials (RCTs) have compared the efficacy of different vaccine formulations. This study assessed the relative efficacy of different varicella vaccines using network meta-analysis (NMA).

Methods

We estimated the relative efficacies of varicella vaccines and dosing regimens from RCTs using Bayesian NMA. Modeling-based time-series NMA (MBNMA) was performed, accounting for differences in time since vaccination, to extrapolate long-term vaccine efficacy (VE).

Results

Eight RCTs were included based on systematic review of biomedical databases. Efficacy data were reported for four varicella-containing vaccines: Varivax (V-MSD, one and two dose), Varilrix (V-GSK, one dose), Priorix-Tetra (MMRV-GSK, one dose), and Sinovac (V-Sinovac, one dose). All varicella vaccines were effective versus no vaccination. Two-dose V-MSD (98.29%, 95% credible interval [CrI] 96.08–99.23) showed significantly higher VE versus all one-dose varicella-containing vaccines, but no significant difference versus two-dose MMRV-GSK (95.19%, 95% CrI 90.3–97.63). Two-dose MMRV-GSK showed higher VE than one-dose V-GSK (66.47%; 95% CrI 43.02–79.43), but no significant differences in VE versus one-dose V-MSD or one-dose V-Sinovac. In one-dose comparisons, V-MSD showed significantly higher VE (93.09%, 95% CrI 89.13–95.96) than V-GSK, but no significant difference versus V-Sinovac (89.22%; 95% CrI 67.1–96.5). MBNMA indicated that protection against varicella was sustained without waning over the 10 year follow-up.

Conclusions

Our study reported higher VE for two-dose V-MSD and MMRV-GSK. Among one-dose formulations, one-dose V-MSD was more efficacious than one-dose V-GSK. Policymakers should take into consideration differences in VE when implementing one- versus two-dose strategies in universal vaccination programs.

Keywords:

• Network meta-analysis
• varicella vaccines
• systematic literature review
• vaccine effectiveness

Transparency

Declaration of funding

This work was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc. The study sponsor participated in the study design, data interpretation and manuscript preparation (author: M.P.).

Declaration of financial/other relationships

M.P. has disclosed that she is an employee and stakeholder of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc. M.K.S., J.T. and A.S. have disclosed that they are employees of Parexel International. J.F. has disclosed that he is a speaker for Merck and Merck Sharp & Dohme LLC, and a member of Merck’s Pediatric Vaccines Advisory Board. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conceptualization: M.P., M.K.S., J.T. and J.F. Methodology: M.P., M.K.S., J.T. and J.F. Software: M.K.S., J.T. and A.S. Validation: M.K.S., J.T. and A.S. Formal analysis: M.K.S., J.T. and A.S. Investigation: M.K.S., J.T. and A.S. Resources: M.P. Data curation: M.K.S., J.T. and A.S. Writing, review and editing: M.P., M.K.S., J.T., A.S. and J.F. Visualization: M.P., M.K.S., J.T., A.S. and J.F. Supervision: M.P. Project administration: M.K.S. Funding acquisition: M.P.

Acknowledgements

The authors would like to acknowledge Dr. Lara Wolfson for her contributions on initiating the study concept, design and feasibility analysis. They would like to acknowledge Dr. Barbara Kuter, Dr. Se Li, and Taylor Gandy for their support during the literature review process and feasibility analysis. Editorial assistance was provided by Bill Wolvey at Parexel International, with funding from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. Inc. Part of this research was presented at the European Society for Paediatric Infectious Diseases Virtual Meeting, 2020 Oct 26–29.

Notes

i Varivax is a registered trade name of Merck & Co. Inc.

ii Varilrix is a registered trade name of GSK

iii Priorix-Tetra is a trade name of GSK

iv Sinovac is a registered trade name of Sinovac Biotech Ltd