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

This article is related to:

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

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

Dear Editor,

We thank S. Hadigal and his colleagues from Viatris for their interest in our paper. We are also grateful for the opportunity to address the comments their raised in their letter regarding our study “Cost-effectiveness of influenza vaccination with a high dose quadrivalent vaccine of the elderly population in Belgium, Finland, and Portugal”. Our paper shows, under three different settings, that switching from standard-dose (SDQIV) to high-dose quadrivalent vaccine (HDQIV) would reduce the burden of seasonal influenza while being a cost-effective intervention [1].

As expressed by Hadigal et al. we similarly recognize the importance of feeding the economic models with robust input values in order to appropriately inform decision makers [2]. To fulfill this imperative, throughout our history of dossier submissions for HD-QIV in Europe, we have worked jointly with influenza experts to validate each input value. Whenever possible, we also sought feedback from relevant HTA bodies and NITAGs whom would assess the dossiers. Nevertheless, the inherent variability of influenza outbreaks, in addition to differences in surveillance methods from country to country render it near impossible to reach a consensus as to the best source for many of the country epidemiological inputs. With this background, we would like to take this opportunity to provide more detailed justification on our choices for the inputs challenged by Hadigal et al. [3].

Regarding the relative efficacy (rVE) of HDQIV compared to SDQIV, Hadigal et al. [3] suggested to use a rVE from an abstract of a congress communication, which was not yet available when our evaluations were made. Nevertheless, a similar systematic review was available [4] at the time the dossiers were submitted, in which HDQIV demonstrated better protection (rVE = 19.5% [8.6–29.0%]) against influenza-like illness (ILI). Instead, the source we used in Alvarez et al. [1] for rVE arises from an efficacy randomized clinical trial on the prevention of laboratory confirmed influenza cases (and not ILI). These efficacy data were considered in the assessment by the European Heads of Medicines Agencies (HMA) that evaluated the benefits of HDQIV [5].

With respect to the influenza attack rate we used, we acknowledge it has some caveats (like other inputs of influenza models), but for the modeling purposes, we needed an attack rate in a completely unvaccinated population. Therefore, despite the limitations of Somes et al. [6], this was the best source available. As we were conscious of the issues with this input, we used a stepwise approach to estimate the number of influenza cases and the number of hospitalizations, for which there are more precise sources at country level. As the latter are the main driver for cost-effectiveness, the impact of the influenza attack rate proved to be minimal (e.g. changing the attack rate from 7.2% to 3.9% result in ICERs slightly higher, from 1397 to 2619 €/QALY for Belgium; from 9581 to 10,749 €/QALY for Finland; and from 15,267 to 15,663 €/QALY for Portugal).

Finally, the topic of the measured burden of influenza is a matter of ongoing discussion. It is widely acknowledged that when measured only by laboratory diagnosis, the full burden of influenza is underestimated [7], but it is difficult to precisely ascertain burden as a fraction of respiratory infections due to influenza, referred to as “broad influenza”. In the economic assessments we performed, the broader hospitalization definition slightly changed from country to country depending on data availability and local experts’ advice, to provide the better picture of the protection provided by HDQIV. The resulting ICERs are indeed lower than those that would be obtained for laboratory-confirmed influenza cases, but the latter would represent an extremely conservative approach, underestimating the true benefit of HDQIV, as it was acknowledged by the evaluating HTA bodies.

We addressed the various scenarios suggested by the responding authors, and none of them impacted the study’s overall conclusion – switching from standard-dose (SDQIV) to high-dose quadrivalent vaccine (HDQIV) among adults ≥65 years would reduce the burden of seasonal influenza, while being a cost-effective intervention.

Transparency

Author contributions

Drafting: FPA

Conceptualization; Review: FPA, HB, CM, AS, TS, CP, CC

Declaration of financial/other relationships

FPA, HB, CM, AS, CP, and CC are employees of Sanofi, which manufactures HD-QIV. They may/may not hold shares in the company.

TS received consulting fees from Sanofi to conduct the country adaptations of the economic model.

Data availability statement

This is a letter to the Editor. Access to the original data is available as per the original article.

Additional information

Funding

No funding was received to produce this letter to the editor.