Reply letter to “Cost-effectiveness of influenza vaccination with a high dose quadrivalent vaccine of the elderly population in Belgium, Finland, and Portugal”

This article is related to:

Reply to letter by Hadigal et al. regarding the cost-effectiveness of high dose quadrivalent vaccine in three European countries

Dear Editor,

We read with interest the article from Alvarez FP et al.¹ concluding that switching to a high-dose quadrivalent influenza vaccine (HDQIV) from a standard-dose quadrivalent influenza vaccine (SDQIV) is cost-effective and contributes to a significant improvement in influenza health outcomes (reduction of flu-related cases/hospitalizations/deaths and physician and emergency department visits). However, we have made a few observations on some of the assumptions/conclusions put forward in the publication.

First, the relative vaccine efficacy (rVE) of HDQIV compared to SDQIV was assumed to be 24.2% and was taken from a study comparing trivalent formulations in the 2011 to 2013 season². We believe that a more practical number would be 14.3%, taken from the latest systematic review analysis³.

Second, the study estimated the number of influenza cases based on attack rate, vaccine coverage and vaccine efficacy for each vaccine strategy. The attack rate assumed was 7.2% based on a study conducted by Somes MP et al.⁴, where the attack rate was pooled from three heterogenous studies that were conducted in different seasons/countries. Also, the attack rate of 7.2% would lead to an absolute vaccine effectiveness of 74% for SD trivalent influenza vaccine in the HD trivalent influenza vaccine trial as mentioned in a previous article.⁵ This is not a realistic number for any age group, and especially for elderly population where the vaccine efficacy is known to be lower⁵. It is important to note that the WHO reference of 5-10% attack rate used was of 2019, while the rVE used was taken from 2011 to 2013 season.

The attack rates vary between age groups, and there are big differences reported in the literature. A study conducted by Tokars JI et al.⁶ reported attack rates of 3.9% for the elderly. Using the attack rates of 3.9%, the benefit of HDQIV would be less impactful.

Forth and finally, the authors’ results rely in part on the adjusting upwards the influenza cases and the subsequent mortalities. Because the influenza virus may cause pneumonia, the authors included both influenza- and pneumonia-related hospitalizations when estimating the hospitalization rate potentially linked to influenza. However, it is not always the case and this “influenza broad definition” may overstate the potential size of the base-level burden and overstate the benefit of using the HDQIV, as there are fewer savings to be had from any improvement in the efficacy. An alternative assumption to present results without this broader definition would have given a better picture of the cost-utility results. The authors note that “including a broader hospitalization definition, lead to a greater incremental hospitalization cost”; however, they do not tell us whether their results are fundamentally changed in the sense of being cost-effective or not by the use of a broader definition that includes both pneumonia and influenza.

Given these concerns, we believe that further work is needed to refine and validate the health economic model before the results can be considered robust and reliable. We appreciate the contribution of the authors in this area.

Transparency

Declaration of funding

No funding was received to produce this article.

Declaration of financial/other relationships

SH, LC and JC are the employees of Viatris. Authors have no other competing interest to declare.

Author contributions

All the authors meet the ICMJE criteria for authorship. All authors were involved in conceptualization, data analysis, writing the draft and approved the final submitted version of the manuscript.

Acknowledgements

Not applicable.