https://orcid.org/0000-0003-3085-6275
Dear Dr. Ellis,
We read with interest the recent cost-effectiveness analysis (CEA) published by Ruiz-Aragón et al., 2020,Citation1 concluding: “QIVc [Flucelvax] offers a cost-effective alternative to QIVe [egg-manufactured influenza vaccine] and should be considered as an alternative vaccine to QIVe for people aged 9–64 at high risk of influenza complications in Spain”.
As a cost-effectiveness analysis (CEA) measures the incremental health gains and costs of interventions, results are highly sensitive to assumptions of benefit. For this reason, WHO recommends vaccine effectiveness (VE) estimates should be based upon systematic reviews or meta-analyses; or use a range of values, subject to sensitivity analyses representative of extreme circumstances.Citation2 ISPOR guidelines insist on a comprehensive and transparent approach to select input data from the best available, evidence-based source.Citation3 Husereau et al. state that if single study effectiveness source is used, the design features must be fully explained and justified.Citation4
This analysis by Ruiz-Aragón et al. is based on a single point relative vaccine effectiveness (rVE) from Boikos et al., 2019,Citation5 and therefore met none of these criteria above. While we focus here on health economic guidelines, the study from Boikos et al. is also flawed from a design perspective for several reasons (nonspecific outcomes; single season; unclear methods) and is notable mainly for the very high rVE reported. Indeed, to further support our position that the health economic model is flawed and is driven by bias toward high rVE estimates, the vaccine effectiveness used for 18–65 year old (26.8%) has been applied to those aged 9–18 years, yet the Boikos study referred to in their model reports only 18.8% for 4–17 year olds, and this did not reach statistical significance.
These limitations were avoidable as at least five other studies describing effectiveness of cell-manufactured vs. egg-manufactured vaccines have been completed, and four of these have been published in peer-reviewed journals.Citation6–10 These studies demonstrate no consistent trend in results favoring cell-manufactured over egg-manufactured vaccines.
The omission by Ruiz-Aragón et al. of these data points in favor of a single rVE estimate does not fit the minimal standards for CEA analysis,Citation2–4 provides a distorted view of the relative health economic attributes of the vaccines under analysis and prevents readers from taking an unbiased view of the relative health economic merits of egg- and cell-manufactured influenza vaccines.
Sincerely yours,
Disclosure of potential conflicts of interest
AP, FA, JN, RH, and JLLB work for Sanofi Pasteur, a company which makes influenza vaccines.
References
- Ruiz-Aragón J, Gani R, Márquez S, Alvarez P. Estimated cost-effectiveness and burden of disease associated with quadrivalent cell-based and egg-based influenza vaccines in Spain. Hum Vaccin Immunother. published online February 10, 2020;2020:1–7. doi:10.1080/21645515.2020.1712935.
- Word Health Organization. WHO guide for standardization of economic evaluations of immunization programmes. 2nd ed. Geneva (Switzerland): World Health Organization; 2019. Available at https://www.who.int/immunization/documents/who_ivb_19.10/en/
- Mauskopf J, Standaert B, Connolly MP, Culyer AJ, Garrison LP, Hutubessy R, Jit M, Pitman R, Revill P, Severens JL. Economic Analysis of Vaccination Programs: An ISPOR Good Practices for Outcomes Research Task Force Report. Value in Health. 2018;21:1133–49. doi:10.1016/j.jval.2018.08.005
- Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, Augustovski F, Briggs AH, Mauskopf J, Loder E. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMC Medicine 2013;11:80. doi:10.1186/1741-7015-11-80
- Boikos C, Sylvester GC, Sampalis JS, Mansi JA. Relative effectiveness of the cell-cultured quadrivalent influenza vaccine compared to standard, egg-derived quadrivalent influenza vaccines in preventing influenza-like illness in 2017–2018. Clin Infect Dis. 2020; published online April 7, 2020. doi:10.1093/cid/ciaa371
- DeMarcus L, Shoubaki L and Federinko S. Comparing influenza vaccine effectiveness between cell-derived and egg-derived vaccines, 2017-2018 influenza season. Vaccine. 2019;37:4015–21.
- Izurieta HS, Chillarige Y, Kelman J, Wei Y, Lu Y, Xu W, Lu M, Pratt D, Chu S, Wernecke M, MaCurdy T, Forshee R. Relative Effectiveness of Cell-Cultured and Egg-Based Influenza Vaccines Among Elderly Persons in the United States, 2017–2018. J Infect Dis. 2019; 220:1255–64. doi:10.1093/infdis/jiy716
- Izurieta HS, Chillarige Y, Kelman J, Wei Y, Lu Y, Xu W, Lu M, Pratt D, Wernecke M, MaCurdy T, Forshee R. Relative Effectiveness of Influenza Vaccines Among the United States Elderly, 2018–2019. J of Infect Dis. 2020;222:278–87. doi:10.1093/infdis/jiaa080
- Klein NP, Fireman B, Goddard K, Zerbo O, Asher J, Zhou J, King J, Lewis N. Vaccine effectiveness of flucelvax relative to inactivated influenza vaccine during the 2017-18 influenza season in Northern California. Presented at: lnfectious Disease (ID) Week Congress; 2020 Oct 6. San Francisco (CA). Available at https://idsa.confex.com/idsa/2018/webprogram/Paper74111.html
- Bruxvoort KJ, Luo Y, Ackerson B, Tanenbaum HC, Sy LS, Gandhi A, Tseng HF. Comparison of vaccine effectiveness against influenza hospitalization of cell-based and egg-based influenza vaccines, 2017–2018. Vaccine. 2019;37(39):5807–11. doi:10.1016/j.vaccine.2019.08.024.